High-Throughput Method of Whole-Brain Sectioning, Using the Tape-Transfer Technique

Cryostat sectioning is a popular but labor-intensive method for preparing histological brain sections. We have developed a modification of the commercially available CryoJane tape collection method that significantly improves the ease of collection and the final quality of the tissue sections. The key modification involves an array of UVLEDs to achieve uniform polymerization of the glass slide and robust adhesion between the section and slide. This report presents system components and detailed procedural steps, and provides examples of end results; that is, 20mum mouse brain sections that have been successfully processed for routine Nissl, myelin staining, DAB histochemistry, and fluorescence. The method is also suitable for larger brains, such as rat and monkey

Abnormal oscillatory brain dynamics in schizophrenia: a sign of deviant communication in neural network?

<p>Abstract</p> <p>Background</p> <p>Slow waves in the delta (0.5–4 Hz) frequency range are indications of normal activity in sleep. In neurological disorders, focal electric and magnetic slow wave activity is generated in the vicinity of structural brain lesions. Initial studies, including our own, suggest that the distribution of the focal concentration of generators of slow waves (dipole density in the delta frequency band) also distinguishes patients with psychiatric disorders such as schizophrenia, affective disorders, and posttraumatic stress disorder.</p> <p>Methods</p> <p>The present study examined the distribution of focal slow wave activity (ASWA: abnormal slow wave activity) in116 healthy subjects, 76 inpatients with schizophrenic or schizoaffective diagnoses and 42 inpatients with affective (ICD-10: F3) or neurotic/reactive (F4) diagnoses using a newly refined measure of dipole density. Based on 5-min resting magnetoencephalogram (MEG), sources of activity in the 1–4 Hz frequency band were determined by equivalent dipole fitting in anatomically defined cortical regions.</p> <p>Results</p> <p>Compared to healthy subjects the schizophrenia sample was characterized by significantly more intense slow wave activity, with maxima in frontal and central areas. In contrast, affective disorder patients exhibited less slow wave generators mainly in frontal and central regions when compared to healthy subjects and schizophrenia patients. In both samples, frontal ASWA were related to affective symptoms.</p> <p>Conclusion</p> <p>In schizophrenic patients, the regions of ASWA correspond to those identified for gray matter loss. This suggests that ASWA might be evaluated as a measure of altered neuronal network architecture and communication, which may mediate psychopathological signs.</p

The Power Board of the KM3NeT Digital Optical Module: design, upgrade, and production

The KM3NeT Collaboration is building an underwater neutrino observatory at the bottom of the Mediterranean Sea consisting of two neutrino telescopes, both composed of a three-dimensional array of light detectors, known as digital optical modules. Each digital optical module contains a set of 31 three inch photomultiplier tubes distributed over the surface of a 0.44 m diameter pressure-resistant glass sphere. The module includes also calibration instruments and electronics for power, readout and data acquisition. The power board was developed to supply power to all the elements of the digital optical module. The design of the power board began in 2013, and several prototypes were produced and tested. After an exhaustive validation process in various laboratories within the KM3NeT Collaboration, a mass production batch began, resulting in the construction of over 1200 power boards so far. These boards were integrated in the digital optical modules that have already been produced and deployed, 828 until October 2023. In 2017, an upgrade of the power board, to increase reliability and efficiency, was initiated. After the validation of a pre-production series, a production batch of 800 upgraded boards is currently underway. This paper describes the design, architecture, upgrade, validation, and production of the power board, including the reliability studies and tests conducted to ensure the safe operation at the bottom of the Mediterranean Sea throughout the observatory's lifespa

Ability of Granger Causality Analysis to Detect Indirect Links: A Simulation Study

Granger causality (G-causality) has emerged as a useful tool to investigate the influence that one system can exert over another system, but challenges remain when applying it to biological data. Specifically, it is not clear if G-causality can distinguish between direct and indirect influences. In this study time domain G-causality connectivity analysis was performed on simulated electroencephalographic cerebral signals. Conditional multivariate autoregressive model was applied to 19 virtual time series (nodes) to identify the effects of direct and indirect links while varying one of the following variables: the length of the time series, the lags between interacting nodes, the connection strength of the links, and the noise. Simulated data revealed that weak indirect influences are not identified by Gcausality analysis when applied on covariance stationary, non-correlated electrophysiological time series

Cryptogenic stroke and atrial fibrillation in a real-world population: the role of insertable cardiac monitors

The incidence of atrial fibrillation (AF) in cryptogenic stroke (CS) patients has been studied in carefully controlled clinical trials, but real-world data are limited. We investigated the incidence of AF in clinical practice among CS patients with an insertable cardiac monitor (ICM) placed for AF detection. Patients with CS admitted to our Stroke Unit were included in the study; they received an ICM and were monitored for up to 3 years for AF detection. All detected AF episodes of at least 120 sec were considered. From March 2016 to March 2019, 58 patients (mean age 68.1 ± 9.3 years, 67% male) received an ICM to detect AF after a CS. No patients were lost to follow-up. AF was detected in 24 patients (41%, AF group mean age 70.8 ± 9.4 years, 62% male) after a mean time of 6 months from ICM (ranging from 2 days to 2 years) and 8 months after CS (ranging from 1 month to 2 years). In these AF patients, anticoagulant treatment was prescribed and nobody had a further stroke. In conclusion, AF episodes were detected via continuous monitoring with ICMs in 41% of implanted CS patients. AF in CS patients is asymptomatic and difficult to diagnose by strategies based on intermittent short-term recordings. Therefore, we suggest that ICMs should be part of daily practice in the evaluation of CS patients

A low-cost technique to cryo-protect and freeze rodent brains, precisely aligned to stereotaxic coordinates for whole-brain cryosectioning

A major challenge in the histological sectioning of brain tissue is achieving accurate alignment in the standard coronal, horizontal, or sagittal planes. Correct alignment is desirable for ease of subsequent analysis and is a prerequisite for computational registration and algorithm-based quantification of experimental data. We have developed a simple and low-cost technique for whole-brain cryosectioning of rodent brains that reliably results in a precise alignment of stereotactic coordinates. The system utilises a 3-D printed model of a mouse brain to create a tailored cavity that is used to align and support the brain during freezing. The alignment of the frozen block is achieved in relation to the fixed edge of the mould. The system also allows for two brains to be frozen and sectioned simultaneously. System components, procedural steps, and examples of the end results are presented

EEG Markers of Dementia with Lewy Bodies:A Multicenter Cohort Study

Quantitative EEG (QEEG) has demonstrated good discriminative capacity for dementia with Lewy bodies (DLB) diagnosis as compared to Alzheimer's disease (AD) with a predictive value of 100 in a single cohort study. EEG in DLB was characterized by a dominant frequency (DF) in pre-alpha (5.5-7.5Hz), theta, or delta bands and DF variability (DFV) &gt;1.2Hz, frequency prevalence (FP) pre-alpha in &gt;40 and FP alpha in &lt;32 of the epochs. To validate the aforementioned QEEG findings in independent cohorts of clinically diagnosed DLB versus AD patients, we analyzed EEG traces of 79 DLB and 133 AD patients (MMSE &gt;20) collected from four European Centers. EEG traces from 19 scalp derivations were acquired as at least 10min continuous signals and epoched in off-setting as series of 2-second-long epochs, subsequently processed by Fast Fourier Transform (frequency resolution 0.5Hz). DLB patients showed EEG specific abnormalities in posterior derivations characterized by DF &lt;8Hz FP pre-alpha &gt;50, FP alpha &lt;25. DFV was &gt;0.5Hz. AD patients displayed stable alpha DF, DFV &lt;0.5Hz, FP pre-alpha &lt;30, and FP alpha &gt;55. DLB and AD differed for DF (p&lt;10-6), DFV (p&lt;0.05), FP pre-alpha (p&lt;10-12) and FP alpha (p&lt;10-12). Discriminant analysis detected specific cut-offs for every EEG mathematical descriptor; DF=8, DFV=2.2Hz, FP pre-alpha=33, FP alpha=41 for posterior derivations. If at least one of the cut-off values was met, the percentage of DLB and AD patients correctly classified was 90 and 64, respectively. The findings in this multicenter study support the validity of QEEG analysis as a tool for diagnosis in DLB patients

Anterior EEG slowing in dementia with Lewy bodies: a multicenter European cohort study

Electroencephalography (EEG) slowing with prealpha dominant frequency (DF) in posterior derivations is a biomarker for dementia with Lewy bodies (DLB) diagnosis, in contrast with Alzheimer's disease (AD). However, an intrasubject re-evaluation of the original data, which contributed to the identification of EEG DLB biomarker, showed that DF was slower in anterior than posterior derivations. We suppose this anterior-posterior gradient of DF slowing could arise in DLB from a thalamocortical dysrhythmia, differently involving the anterior and posterior cortical areas, and correlating with cognitive impairment (Mini-Mental State Examination). EEG was recorded in 144 DLB, 116 AD, and 65 controls from 7 Centers of the European DLB Consortium. Spectra were divided into delta, theta, prealpha, alpha frequency bands. In DLB, mean DF was prealpha both anteriorly and posteriorly, but lower anteriorly (p < 0.001). In 14% of DLB, DF was prealpha anteriorly, whereas alpha posteriorly. In AD and controls, DF was constantly alpha. EEG slowing in DLB correlated with cognitive impairment. Thalamocortical dysrhythmia gives rise to prealpha rhythm with an anterior-posterior gradient and correlates with impaired cognition

Hyperconnectivity in Dementia Is Early and Focal and Wanes with Progression

We investigated in a longitudinal multicenter cohort study functional cortical connectivity changes along the course of frontotemporal dementia (FTD) and Alzheimer's disease (AD) from the prodromal stage of the diseases. Electroencephalography (EEG) was recorded in 18 FTD and 18 AD patients at the prodromal stage of dementia, at dementia onset, and 3 years after dementia onset. Twenty healthy controls (HC) underwent EEG recordings at the same time interval as the patients. Mutual information (MI) analysis measured the strength of functional network connectivity. FTD and AD patients showed greater MI at the prodromal stage of dementia (FTD vs. HC P = 2 × 10-8; AD vs. HC P = 4 × 10-3). Local connectivity was higher in left and right frontal areas of FTD (P = 7 × 10-5 and 0.03) and in left and right posterior areas in AD (P = 3 × 10-5 and 5 × 10-5) versus HC. We showed cortical hyperconnectivity at the prodromal stage of dementia in areas involved in the specific pathological process of FTD (frontal regions) and AD (posterior regions). Hyperconnectivity disappeared during follow-up, thus suggesting that it is an early electrophysiological feature of dementia, potentially useful to identify prodromal FTD and AD

Cortical network modularity changes along the course of frontotemporal and Alzheimer's dementing diseases

Cortical network modularity underpins cognitive functions, so we hypothesized its progressive derangement along the course of frontotemporal (FTD) and Alzheimer's (AD) dementing diseases. EEG was recorded in 18 FTD, 18 AD, and 20 healthy controls (HC). In the FTD and AD patients, the EEG recordings were performed at the prodromal stage of dementia, at the onset of dementia, and three years after the onset of dementia. HC underwent three EEG recordings at 2\u20133-year time interval. Information flows underlying EEG activity recorded at electrode pairs were estimated by means of Mutual Information (MI) analysis. The functional organization of the cortical network was modelled by means of the Graph theory analysis on MI adjacency matrices. Graph theory analysis showed that the main hub of HC (Parietal area) was lost in FTD patients at onset of dementia, substituted by provincial hubs in frontal leads. No changes in global network organization were found in AD. Despite a progressive cognitive impairment during the FTD and AD progression, only the FTD patients showed a derangement in the cortical network modularity, possibly due to dysfunctions in frontal functional connectivity