Biology subjects

Bartsch, H.

Publications and source records attributed to Bartsch, H..

6 recordsLinked to original sources

bioRxiv2025

Seizure-induced Transient Disruptive Changes in Brain Microstructure

A leading hypothesis for the mechanisms of electroconvulsive therapy (ECT) posits an initial disruptive effect followed by enhanced neuroplasticity. However, direct evidence of the presumed early disruptive changes, potentially driven by seizures, remains limited. This study examined longitudinal changes in multishell diffusion MRI-derived metrics in 25 individuals with depression, with scans acquired two hours before and after their first ECT session. Follow-up scans were collected within 14 days and 6 months after the last ECT session. To control for potential confounding effects of anesthesia and repeated measurements, two additional groups were included: 16 individuals undergoing short-acting anesthesia and 16 healthy controls without interventions. A multicompartment model was applied to explore extracellular free water and microstructures in the intracellular/extracellular compartments. Whole-brain voxel-wise analyses identified a pattern consistent with vasogenic edema (e.g., increased extracellular free water) in widespread bilateral brain regions following a single ECT session. Increases in brain tissue free water were significantly correlated with electrical stimulus charge (r=0.51, p=0.01) but not with post-ictal reorientation time (r=0.11, p=0.92). These changes were not observed in either control group. Follow-up assessments confirmed that the alterations in tissue free water resolved within 14 days. A single ECT-induced seizure induces transient, reversible changes consistent with vasogenic edema, rather than irreversible cellular injury typically associated with cytotoxic edema. These reversible changes may represent an initial disruptive phase that facilitates subsequent adaptive brain responses, including neuroplasticity and network reorganization underlying the therapeutic effects of ECT.

neuroscience↗

bioRxiv2022

Male and Female Brain Coherence Models of Cognitive Performance and Psychopathology

Finding reliable imaging biomarkers of mental illness has been a major challenge, on a par with the quest for biomarkers of the male versus the female brain, as the two types of imaging inform one another. We explored the hypothesis that the degree of coherence (internal isomorphism) between brain volumes of the left versus the right hemisphere for patients with psychopathological conditions follows the brain coherence pattern of the healthy male or healthy female. We developed the distance index (DI) as a biomarker of brain coherence and compared it with three ad hoc coherence measures. We found that only DI could reliably distinguish males from females and patients from controls. Also, cortical regions with highest DI scores were swapped between males and females across groups following male/female models of psychopathology. Furthermore, although indices were similar in predicting cognitive performance, DI provided a more proportionate prediction pattern across diagnosis groups, and more robust interactions with males/females. These findings highlight the importance of brain coherence, particularly measured by DI, for phenotyping sex and mental illness.

neuroscience↗

bioRxiv2021

Neural excitation/inhibition imbalance and the treatment of severe depression

An influential hypothesis holds that depression is related to a neural excitation/inhibition imbalance, but its role in the treatment of depression remains unclear. Here, we show that unmedicated patients with severe depression demonstrated reduced inhibition of brain-wide resting-state networks relative to healthy controls. Patients using antidepressants showed inhibition that was higher than unmedicated patients and comparable to controls, but they still suffered from severe depression. Subsequent treatment with electroconvulsive therapy (ECT) reduced depressive symptoms, but its effectiveness did not depend on changes in network inhibition. Concomitant pharmacotherapy increased the effectiveness of ECT, but only when the strength of neural inhibition before ECT was within the normal range and not when inhibition was excessive. These findings suggest that reversing the excitation/inhibition imbalance may not be sufficient nor necessary for the effective treatment of severe depression, and that brain-state informed pharmacotherapy management may enhance the effectiveness of ECT.

neuroscience↗

bioRxiv2021

Heterogeneity in PHGDH protein expression potentiates cancer cell dissemination and metastasis

Cancer metastasis requires the transient activation of cellular programs enabling dissemination and seeding in distant organs. Genetic, transcriptional and translational intra-tumor heterogeneity contributes to this dynamic process. Beyond this, metabolic intra-tumor heterogeneity has also been observed, yet its role for cancer progression remains largely elusive. Here, we discovered that intra-tumor heterogeneity in phosphoglycerate dehydrogenase (PHGDH) protein expression drives breast cancer cell dissemination and metastasis formation. Specifically, we observed intra-tumor heterogeneous PHGDH expression in primary breast tumors, with low PHGDH expression being indicative of metastasis in patients. In mice, Phgdh protein, but not mRNA, expression is low in circulating tumor cells and early metastatic lesions, leading to increased dissemination and metastasis formation. Mechanistically, low PHGDH protein expression induces an imbalance in glycolysis that can activate sialic acid synthesis. Consequently, cancer cells undergo a partial EMT and show increased p38 as well as SRC phosphorylation, which activate cellular programs of dissemination. In turn, inhibition of sialic acid synthesis through knock-out of cytidine monophosphate N-acetylneuraminic acid synthetase (CMAS) counteracts the increased cancer cell dissemination and metastasis induced by low PHGDH expression. In conclusion, we find that heterogeneity in PHGDH protein expression promotes cancer cell dissemination and metastasis formation.

cancer biology↗

bioRxiv2020

Meaningful Effects in the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development (ABCD) Study is the largest single-cohort prospective longitudinal study of neurodevelopment and childrens health in the United States. A cohort of n= 11,880 children aged 9-10 years (and their parents/guardians) were recruited across 22 sites and are being followed with in-person visits on an annual basis for at least 10 years. The study approximates the US population on several key sociodemographic variables, including sex, race, ethnicity, household income, and parental education. Data collected include assessments of health, mental health, substance use, culture and environment and neurocognition, as well as geocoded exposures, structural and functional magnetic resonance imaging (MRI), and whole-genome genotyping. Here, we describe the ABCD Study aims and design, as well as issues surrounding estimation of meaningful associations using its data, including population inferences, hypothesis testing, power and precision, control of covariates, interpretation of associations, and recommended best practices for reproducible research, analytical procedures and reporting of results.

neuroscience↗

bioRxiv2018

Image processing and analysis methods for the Adolescent Brain Cognitive Development Study

The Adolescent Brain Cognitive Development (ABCD) Study is an ongoing, nationwide study of the effects of environmental influences on behavioral and brain development in adolescents. The ABCD Study is a collaborative effort, including a Coordinating Center, 21 data acquisition sites across the United States, and a Data Analysis and Informatics Center (DAIC). The main objective of the study is to recruit and assess over eleven thousand 9-10-year-olds and follow them over the course of 10 years to characterize normative brain and cognitive development, the many factors that influence brain development, and the effects of those factors on mental health and other outcomes. The study employs state-of-the-art multimodal brain imaging, cognitive and clinical assessments, bioassays, and careful assessment of substance use, environment, psychopathological symptoms, and social functioning. The data will provide a resource of unprecedented scale and depth for studying typical and atypical development. Here, we describe the baseline neuroimaging processing and subject-level analysis methods used by the ABCD DAIC in the centralized processing and extraction of neuroanatomical and functional imaging phenotypes. Neuroimaging processing and analyses include modality-specific corrections for distortions and motion, brain segmentation and cortical surface reconstruction derived from structural magnetic resonance imaging (sMRI), analysis of brain microstructure using diffusion MRI (dMRI), task-related analysis of functional MRI (fMRI), and functional connectivity analysis of resting-state fMRI.\n\nHighlightsO_LIAn overview of the MRI processing pipeline for the ABCD Study\nC_LIO_LIA discussion on the challenges of large, multisite population studies\nC_LIO_LIA methodological reference for users of publicly shared data from the ABCD Study\nC_LI

neuroscience↗