Biology subjects

Lindner, M.

Publications and source records attributed to Lindner, M..

22 records · Page 2Linked to original sources

bioRxiv2018

Inter-slice leakage and intra-slice aliasing in simultaneous multi-slice echo-planar images

Simultaneous multi-slice (SMS) imaging is a popular technique for increasing acquisition speed in echo-planar imaging (EPI) fMRI. However, SMS data are prone to motion sensitivity and slice leakage artefacts, which spread signal between simultaneously acquired slices. Relevant to motion sensitivity, artefacts from moving anatomic structures propagate along the phase-encoding (PE) direction. This is particularly relevant for eye movement. As signal from the eye is acquired along with signal from simultaneously excited slices during SMS, there is potential for signal to spread in-plane and between spatially remote slices. After identifying an artefact temporally coinciding with signal fluctuations in the eye and spatially distributed in correspondence with multiband slice acceleration and parallel imaging factors, we conducted a series of small experiments to investigate eye movement artefacts in SMS data and the contribution of PE direction to the invasiveness of these artefacts. Five healthy adult volunteers were scanned during a blinking task using a standard SMS-EPI protocol with posterior-to-anterior (P>>A), anterior-to-posterior (A>>P) or right-to-left (R>>L) PE direction. The intensity of signal fluctuations (artefact severity) was measured at expected artefact positions and control positions. We demonstrated a direct relationship between eye movements and artefact severity across expected artefact regions. Within-brain artefacts were apparent in P>>A- and A>>P-acquired data but not in R>>L data due to the shift in artefact positions. Further research into eye motion artefacts in SMS data is warranted but researchers should exercise caution with SMS protocols. We recommend rigorous piloting of SMS protocols and switching to R>>L/L>>R PE where feasible.

neuroscience↗

bioRxiv2018

Quality assessment of tissue samples stored in a specialized human lung biobank

Human sample, from patients or healthy donors, are a valuable link between basic research and clinic. Especially in translational research, they play an essential role in understanding development and progression of diseases as well as in developing new diagnostic and therapeutic tools. Stored in biobanks, fast access to appropriate material becomes possible. However, biobanking in a clinical context faces several challenges. In practice, collecting samples during clinical routine does not allow to strictly adhere to protocols of sample collection in all aspects. This may influence sample quality to variable degrees. Time from sample draw to asservation is a variable factor, and influences of prolonged storage at ambient temperature of tissues are not well understood. We investigated whether delays between 5 minutes and 3 hours, and the use of RNAlater RNA-preserving reagent would lead to a relevant drop in sample quality, measured by quantitative mRNA expression analysis. Our findings suggest that even under ambient conditions, delays up to 3 hours do not have a major impact on sample quality as long as the tissue remains intact.

molecular biology↗

bioRxiv2018

Regional Striatal Cholinergic Involvement in Human Behavioural Flexibility

Animal studies have shown that the striatal cholinergic system plays a role in behavioural flexibility but, until recently, this system could not be studied in humans due to a lack of appropriate non-invasive techniques. Using proton magnetic resonance spectroscopy (1H-MRS) we recently showed that the concentration of dorsal striatal choline (an acetylcholine precursor) changes during reversal learning (a measure of behavioural flexibility) in humans. The aim of the present study was to examine whether regional average striatal choline was associated with reversal learning. We measured choline at rest in both the dorsal and ventral striatum using 1H-MRS and examined its relationship with performance on a probabilistic learning task with a reversal component. Task performance was described using a simple reinforcement learning model that dissociates the contributions of positive and negative prediction errors to learning. Average levels of choline in the dorsal striatum were associated with performance during reversal, but not during initial learning. Specifically, lower levels of choline in the dorsal striatum were associated with a lower number of perseverative trials. Moreover, choline levels explained inter-individual variance in perseveration over and above that explained by learning from negative prediction errors. These findings suggest that the dorsal striatal cholinergic system plays an important role in behavioural flexibility, in line with evidence from the animal literature and our previous work in humans. Additionally, this work provides further support for the idea of measuring choline with 1H-MRS as a non-invasive way of studying human cholinergic neurochemistry.\n\nSIGNIFICANCE STATEMENTBehavioural flexibility is a crucial component of adaptation and survival, as well as everyday living. Evidence from the animal literature shows the striatal cholinergic system is fundamental to reversal learning, a key paradigm for studying behavioural flexibility. However, this system remains understudied in humans, largely due to a lack of non-invasive techniques. Using proton magnetic resonance spectroscopy (1H-MRS), we showed that choline levels at rest in the dorsal striatum are associated with individual differences in performance specifically during reversal learning. These novel findings help to bridge the gap between animal studies of the striatal cholinergic system and human studies of basal ganglia function, by demonstrating the importance of cholinergic function in the dorsal striatum in human behavioural flexibility. Importantly, the methods described here can not only be applied to furthering our understanding of healthy human neurochemistry, but can also be applied to extending our understanding of cholinergic disorders.

neuroscience↗

bioRxiv2018

Thalamostriatal Interactions in Human Reversal Learning

Cognitive flexibility is crucial for adaptation and is disrupted in neuropsychiatric disorders and psychopathology. Human studies of flexibility using reversal learning tasks typically contrast error trials before and after reversal, which provides little information about the mechanisms that support learning and expressing a new response. However, animal studies suggest a specific role in this latter process for the connections between the dorsal striatum and the centromedian parafascicular (CM-Pf) thalamus, a system which may recruit the striatal cholinergic interneurons, but which is not well understood in humans. This study investigated the role of this system in human probabilistic reversal learning, specifically with respect to learning a new response strategy, contrasting its function to that of the better understood orbitoftontal-striatal systems. Using psychophysiological interaction (PPI) analysis of functional magnetic resonance imaging (fMRI) data we show that connectivity between the striatum and both the lateral orbitofrontal cortex (lOFC) and CM-Pf pathways increased during reversal, but not initial learning. However, while the strength of lOFC-striatal connectivity was associated with the speed of the reversal, the strength of CM-Pf-striatal connectivity was associated specifically with the quality of the reversal (reduced regressive errors). These findings expand our understanding of flexibility mechanisms in the human brain, bridging the gap with animal studies of this system.

neuroscience↗