Biology subjects

Linnman, C.

Publications and source records attributed to Linnman, C..

4 recordsLinked to original sources

bioRxiv2026

Inflections in adolescent cortical maturation signal psychopathology risk

Cerebral cortical maturation supports emotional, social, and cognitive development during adolescence1. Neurodevelopmental theories of psychiatric illnesses, which peak in onset around age 182, implicate subtle alterations in adolescent cortical development3. However, mechanistic links between cortical maturation and emergent psychopathology have remained elusive. This gap likely reflects a need for more nuanced understanding of cortical development4, larger, longitudinal samples powered to detect small effects,5 and more uniform image quality control.6 Using 29,482 structural MRI scans from 11,720 adolescents in the Adolescent Brain Cognitive Development (ABCD) study, we demonstrate reproducible differences in the contour and tempo of maturation across the cortical surface. Regional trajectories are robust to image quality variance and align with increasing functional specialization over time. Thicker cortex in early-maturing sensory regions predicts psychiatric symptoms as early as four years prior to their emergence, a pattern that subsequently spreads to association cortex. Overlap with spatially and temporally organized gene co-expression networks implicates prenatal programming of this sequence of maturation and its links to psychopathology. These findings present a novel, versatile neurodevelopmental framework for cortical maturation during adolescence that sequentially implicates sensory and association cortex in risk for emergent psychiatric symptoms.

neuroscience↗

bioRxiv2024

Imaging demyelinated axons after spinal cord injuries with PET tracer 3F4AP

Spinal cord injuries (SCI) often lead to lifelong disability. Among the various types of injuries, incomplete and discomplete injuries, where some axons remain intact, offer potential for recovery. However, demyelination of these spared axons can worsen disability. Demyelination is a reversible phenomenon, and drugs like 4-aminopyridine (4AP), which target K+ channels in demyelinated axons, show that conduction can be restored. Yet, accurately assessing and monitoring demyelination post-SCI remains challenging due to the lack of suitable imaging methods. In this study, we introduce a novel approach utilizing the positron emission tomography (PET) tracer, [18F]3F4AP, specifically targeting K+ channels in demyelinated axons for SCI imaging. Rats with incomplete contusion injuries were imaged up to one month post-injury, revealing [18F]3F4APs exceptional sensitivity to injury and its ability to detect temporal changes. Further validation through autoradiography and immunohistochemistry confirmed [18F]3F4APs targeting of demyelinated axons. In a proof-of-concept study involving human subjects, [18F]3F4AP differentiated between a severe and a largely recovered incomplete injury, indicating axonal loss and demyelination, respectively. Moreover, alterations in tracer delivery were evident on dynamic PET images, suggestive of differences in spinal cord blood flow between the injuries. In conclusion, [18F]3F4AP demonstrates efficacy in detecting incomplete SCI in both animal models and humans. The potential for monitoring post-SCI demyelination changes and response to therapy underscores the utility of [18F]3F4AP in advancing our understanding and management of spinal cord injuries.

neuroscience↗

bioRxiv2021

Impaired differential learning of fear versus safety signs in obsessive-compulsive disorder

Pavlovian learning mechanisms are of great importance both for models of psychiatric disorders and treatment approaches, but understudied in obsessive-compulsive disorder (OCD). Using an established Pavlovian fear conditioning and reversal procedure, we studied skin conductance responses (SCRs) in 41 patients with OCD and in 32 matched healthy control participants. Within both groups, fear acquisition and reversal effects were evident. When comparing groups, patients showed impaired differential learning of threatening and safe stimuli, consistent with previous research. In contrast to prior findings, differential learning impairments were restricted to fear acquisition, and not observed in the reversal stage of the experiment. As previous and present fear reversal experiments in OCD differed in the use of color coding to facilitate stimulus discrimination, the studies converge to suggest that differential learning of threatening versus safe stimuli is impaired in OCD, but manifests itself differently depending on the difficulty of the association to be learned. When supported by the addition of color, patients with OCD previously appeared to acquire an association early but failed to reverse it according to changed contingencies. In absence of such color coding of stimuli, our data suggest that patients with OCD already show differential learning impairments during fear acquisition, which may relate to findings of altered coping with uncertainty previously observed in OCD. Impaired differential learning of threatening versus safe stimuli should be studied further in OCD, in order to determine whether impairments in differential learning predict CBT treatment outcomes in patients, and whether they are etiologically relevant for OCD.

neuroscience↗

bioRxiv2020

Evaluation of the potassium channel tracer 3F4AP in rhesus macaques

Demyelination causes slowed or failed neuronal conduction and is a driver of disability in multiple sclerosis and other neurological diseases. Currently, the gold standard for imaging demyelination is MRI, but despite its high spatial resolution and sensitivity to demyelinated lesions, it remains challenging to obtain specific and quantitative measures of demyelination. To understand the contribution of demyelination in different diseases and to assess the efficacy of myelin-repair therapies, it is critical to develop new in vivo imaging tools sensitive to changes induced by demyelination. Upon demyelination, axonal K+ channels, normally located underneath the myelin sheath, become exposed and increase in expression, causing impaired conduction. Here, we investigate the properties of the K+ channel PET tracer [18F]3F4AP in primates and its sensitivity to a focal brain injury that occurred three years prior to imaging. [18F]3F4AP exhibited favorable properties for brain imaging including high brain penetration, high metabolic stability, high plasma availability, high reproducibility, high specificity, and fast kinetics. [18F]3F4AP showed preferential binding in areas of low myelin content as well as in the previously injured area. Sensitivity of [18F]3F4AP for the focal brain injury was higher than [18F]FDG, [11C]PiB and [11C]PBR28, and compared favorably to currently used MRI methods.

neuroscience↗