Biology subjects

Aswendt, M.

Publications and source records attributed to Aswendt, M..

7 recordsLinked to original sources

bioRxiv2026

Digital-twin optimized transcranial temporal interference electrical stimulation alters rat brain activity patterns and metabolism including deep structures

Non-invasive deep-brain stimulation (DBS) using transcranial alternating current stimulation (tACS) with temporal interference (TI) has emerged as a promising approach for therapeutic applications in motor and neuropsychiatric disorders. Here, we present a preclinical TI tACS protocol for adult rats that follows a systems approach: an anatomically realistic finite-element digital twin of the rat head is used to optimize electrode placement and injected currents for a deep target, and the model predictions are then tested in vivo. We combine, minimal invasive TI tACS with functional MRI (fMRI) to characterize stimulation-related brain-wide neural responses, alterations in functional connectivity, and changes in neurotransmitter levels. The optimized montage targeted in particular the ventral (motor-related) thalamus. Stimulation-evoked fMRI revealed robust bilateral activation across both subcortical and cortical regions, such as the thalamus, hippocampus, amygdala, retrosplenial and anterior cingulate cortex, which, in turn, reflects direct and indirect activations of brain circuitries by TI tACS. Changes in the connectivity patterns during resting-state fMRI were limited (e.g., fimbria of the hippocampus), but partially overlapped with regional stimulation-evoked fMRI. Therefore, we assume only a short-term influence of TI on neural networks following a single stimulation. MR spectroscopy indicated a trend towards an increased glutamate/GABA ratio in the thalamus. Overall, we demonstrate that TI is a feasible and effective approach for non-invasive DBS in rodents, and that digital twin-based optimization combined with in vivo validation provides a workflow towards individualized stimulation and a foundation for future mechanistic and translational studies in disease models.

neuroscience↗

bioRxiv2026

A harmonized phantom MRI quality control framework identifies sources of longitudinal and multi-site variability

The shift towards open science in preclinical research requires high-quality, comparable data adhering to FAIR principles, yet rigorous quality assurance (QA) and quality control (QC) frameworks remain less established in preclinical magnetic resonance imaging (MRI) than in clinical imaging. To address this limitation, a multicenter study was conducted across 21 international laboratories using standardized commercial liquid phantoms for mouse and rat MRI setups and a harmonized acquisition protocol. Data processing was centralized using AIDAqc, an automated pipeline extracting quantitative metrics including signal-to-noise ratio (SNR), temporal SNR (tSNR), ghost-to-signal ratio (GSR), and motion-equivalent temporal instability, combined with five complementary outlier-detection algorithms. The evaluated datasets encompassed magnetic field strengths from 3.0 to 16.4 T and heterogeneous coil and acquisition configurations. In mouse phantom data, SNR and tSNR were significantly lower at 3 T than at 7 and 9.4 T, whereas artifact-related metrics did not differ significantly between field-strength groups. In rat phantom data, differences between field strengths were less pronounced. At 7 T, substantial dataset-specific differences were observed in anatomical and functional quality metrics, also among datasets using the similar coil configuration. Multicenter reference values for frequently represented 7 T configurations were established, including SNR/tSNR of 48 {+/-} 3/48 {+/-} 1 dB for mouse surface-coil datasets and 49 {+/-} 3/44 {+/-} 4 dB for rat array-coil datasets. Longitudinal anatomical SNR showed generally low variability, whereas ghosting was more variable across time. Automated outlier detection additionally identified transient acquisition instabilities that were not always apparent by visual inspection. Together, these findings show that field strength and nominal coil configuration alone do not adequately characterize MRI performance and support standardized, longitudinal phantom-based QC combined with automated analysis as a practical approach for improving the reliability, transparency, and interoperability of multicenter preclinical MRI data.

bioengineering↗

bioRxiv2026

Structure-function coupling reveals hemisphere-specific network reorganization after stroke

MRI is an excellent tool for monitoring functional and structural network reorganization after brain injury and may provide biomarkers for treatment stratification and novel neuromodulatory interventions. In ischemic stroke, functional network changes, particularly within the contralesional hemisphere, and structural integrity, most prominently of the corticospinal tract, have been successfully associated with behavioral deficit and outcome. However, these components are commonly studied separately and at single time points, which does not reflect the highly dynamic nature of brain network plasticity. Here, we characterized structural and functional connectivity (SC-FC) coupling in the healthy mouse brain and longitudinally assessed intra- and inter-hemispheric connections up to 4 weeks after cortical and cortico-striatal stroke. In the healthy brain, intra-hemispheric SC-FC coupling was lateralized in the sensorimotor network (SMN), whereas the default mode network (DMN) showed no significant hemispheric difference. Intra-hemispheric coupling exceeded inter-hemispheric coupling in the SMN. After cortical stroke, regions with high baseline intra-hemispheric SC-FC coupling remained largely stable, whereas initially weakly coupled sensorimotor regions showed delayed increases within the ischemic hemisphere. Contralesional intra-hemispheric SC-FC coupling changed little, but directional inter-hemispheric analyses revealed selective remodeling, including increased contralesional-to-ischemic coupling of primary motor cortex and reduced bidirectional coupling of medial sensorimotor cortex. Cortico-striatal stroke produced fewer longitudinal changes, dominated by reduced inter-hemispheric motor-cortex coupling. These alterations did not simply correspond to regional lesion involvement. Thus, hemisphere- and direction-resolved SC-FC coupling uncovers network- and stroke-model-specific reorganization not detectable when structural and functional connectivity are analyzed independently.

neuroscience↗

bioRxiv2025

Dynamic structural connectivity changes in cortical and cortico-striatal strokes in mice

Stroke is a primary global health concern, leading to significant mortality and long-term disability. Beyond immediate neuronal damage, functional and structural connectivity is altered brain-wide with implications for functional deficits and recovery. It remains unclear, however, if the level of degeneration, i.e. reduced myelination and axonal damage, as well as compensatory plasticity, i.e., axonal sprouting and remyelination, depend on the lesion size and topology. This study compares for the first time two different stroke models in adult male mice, with the aim of uncovering the dynamics in white matter changes. Repetitive diffusion magnetic resonance imaging (dMRI) over four weeks post photothrombotic cortical (1.41{+/-}0.92% of brain volume), and middle cerebral artery occlusion (MCAO) cortico-striatal (11.53{+/-}2.8% of brain volume), strokes were used to map structural connectivity changes at the whole-brain level. We quantified inter- and intra-hemispheric seed strength changes over time, with seed strength reflecting how strongly each region is connected to the rest of the brain. Differences between groups and time points were assessed using a mixed model corrected for multiple comparisons. In conclusion, large cortico-striatal lesions led to increased structural connectivity in sensorimotor regions, whereas small cortical lesions induced asymmetric connectivity changes: an increase extending globally from the ischemic hemisphere and a decrease expanding globally from the healthy hemisphere. These findings highlight that stroke severity and lesion size significantly affect the temporal dynamics and spatial distribution of connectivity disruptions, emphasizing the need for targeted monitoring of neural changes post-stroke. Significance statementPathophysiological changes close to an ischemic lesion are well understood. But structurally connected regions also undergo stroke-related changes potentially contributing to functional deficits. Animal studies using in vivo diffusion MRI to quantify white matter changes have been limited to single connections, time points after stroke, and basic diffusion measures. We provide the first in-depth characterization of whole-brain fiber tracking to compare small cortical and large cortico-striatal strokes. We found a complex dynamic of decreasing and increasing structural connectivity in single sensorimotor-related brain regions within the brain network - even remote areas from the stroke lesion. This study provides a better understanding of the interactions of regions during stroke recovery, which may help in developing therapies targeting localized white matter repair.

neuroscience↗

bioRxiv2024

Proportional recovery in mice with cortical stroke

The proportional Recovery Rule (PRR) has been frequently used to predict recovery of lost motor function in acute stroke patients. However, it still needs to be explored whether the same concept applies to preclinical, i.e. animal models of stroke recovery. To address this question, we investigated behavioral data from 125 adult male C57Bl/6J mice with photothrombotic strokes in the sensorimotor cortex. Lesion size and location were determined in the first week using in vivo T2-weighted MRI. Motor recovery was evaluated repeatedly over four weeks using the cylinder, grid walk, and rotating beam test. Recovery trajectories were analyzed using a newly formulated Mouse Recovery Rule (MRR), comparing it against the traditional PRR. Initial findings indicated variable recovery patterns, which were separated using a stepwise linear regression approach resulting in two clusters: 47% PRR and 53% MRR. No significant correlation was found between recovery patterns and lesion size or location, suggesting that other biological factors drive individual differences in recovery. Of note, in the MRR cluster, animals recovered to 90% of their initial behavioral state within the first four weeks post-stroke, which is higher than the 70% recovery usually reported in human PRR studies. This study demonstrates the complexity of translating the PRR to stroke recovery models in mice and underscores the need for species-specific recovery models. Our findings have implications for designing and interpreting therapeutic strategies for stroke recovery in preclinical settings, with the potential to improve the predictive accuracy of stroke recovery assessments.

animal behavior and cognition↗

bioRxiv2023

Preserved striatal innervation and motor function despite severe loss of nigral dopamine neurons following mitochondrial dysfunction induced by mtDNA mutations

Degeneration of dopamine neurons in the substantia nigra and their striatal axon terminals causes cardinal motor symptoms of Parkinsons disease (PD). In idiopathic cases, high levels of mitochondrial DNA (mtDNA) mutations associated with mitochondrial dysfunction are a central feature of these vulnerable neurons. Here we present a mouse model expressing the K320E-variant of the mitochondrial helicase Twinkle in dopamine neurons, leading to accelerated mtDNA ageing. K320E-TwinkleDaN mice showed normal motor function at 20 months of age, although already [~]70% of nigral dopamine neurons had perished. The remaining neuron population still preserved [~]75% of axon terminals in the dorsal striatum, which enabled normal dopamine release. Transcriptome analysis and viral tracing confirmed compensatory axonal sprouting of surviving nigral dopamine neurons. We conclude that a small population of substantia nigra neurons can adapt to mtDNA mutations and maintain motor control in mice, holding chances for new treatment strategies in PD patients.

neuroscience↗

bioRxiv2021

Reactive astrocytes prevent maladaptive plasticity after ischemic stroke

Restoration of functional connectivity is a major contributor to functional recovery after stroke. We investigated the role of reactive astrocytes in functional connectivity and recovery after photothrombotic stroke in mice with attenuated reactive gliosis (GFAP-/-Vim-/-). Infarct volume and longitudinal functional connectivity changes were determined by in vivo T2-weighted MRI and resting-state functional MRI. Sensorimotor function was assessed with behavioral tests, and glial and neural plasticity responses were quantified in the peri-infarct region. Four weeks after stroke, GFAP-/-Vim-/- mice showed impaired recovery of sensorimotor function and aberrant restoration of global neuronal connectivity. These mice also exhibited maladaptive plasticity responses, shown by higher number of lost and newly formed functional connections between primary and secondary targets of cortical stroke regions and increased peri-infarct expression of the axonal plasticity marker Gap43. We conclude that reactive astrocytes are required for optimal recovery-promoting plasticity responses after ischemic stroke.

neuroscience↗