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Biology subjects

Fleming, L.

Publications and source records attributed to Fleming, L..

3 recordsLinked to original sources

Increased attentive use leads to more idiosyncratic functional connections

Experience is thought to modify neural connections to adapt the network to be more optimal for the environment. Given the brains complexity, multiple network changes could each move the system toward optimality. Standard methods ignore this multiplicity and examine each connection independently; these studies have often shown considerable inter-individual variability and modest effects (1). Here, we take a different strategy, determining how a whole-brain connection pattern differs from the typical pattern, that is, how idiosyncratic the pattern is. We examined how the idiosyncrasy of whole brain connection patterns varies with frequency of the use of that part of cortex for attention-demanding tasks, focusing on central versus peripheral vision in healthy individuals (where individuals use central vision more frequently for attention-demanding tasks). We found that the whole-brain pattern of functional connections to the cortical representations of central vision is idiosyncratic, whereas patterns of connections to representations of peripheral vision were very similar person-to-person. In a second set of analyses, we examined the brains of people with central vision loss who use a portion of peripheral vision (called the preferred retinal locus) more frequently for attention-demanding tasks in their daily lives. The cortical representation of the preferred retinal locus exhibits more idiosyncratic connections, compared to a control brain region, or compared to the same brain region in matched control participants with healthy vision. These results are consistent with the hypothesis that increased attentive use of a brain area results in idiosyncratic patterns of whole brain connections. Significance StatementWe found that increased attentive use of a brain region results in more idiosyncratic patterns of connections of that region to the rest of the brain. Our findings support the view that V1 retains the capacity for plasticity well beyond the critical period and that these adaptations are idiosyncratic to the individuals experiences. This approach suggests that tailoring personalized rehabilitation plans for individuals with retinal diseases may be more effective than a one size fits all approach. More generally, it offers a promising framework for investigating brain plasticity in both typical and clinical populations, especially in the context of sensory loss and compensatory adaptation.

neuroscience↗

Childhood Maltreatment and Brain Aging During Adulthood

ImportanceChildhood maltreatment (CM) is associated with the early onset of psychiatric and medical disorders and accelerated biological aging. ObjectiveTo identify types of maltreatment and developmental sensitive periods that are associated with accelerated adult brain aging. DesignParticipants were mothers of infants recruited from the community into a study assessing the effects of CM on maternal behavior, infant attachment, and maternal and infant neurobiology. Data were collected from July 2015 to November 2019 and were analyzed from July 2023 to October 2024. SettingAcademic medical centers. ParticipantsHigh-quality MRI scans were obtained on 92 of 150 mothers enrolled in the study. The main exclusion criteria for neuroimaging were histories of head trauma with loss of consciousness or concussion, psychotropic use before age 18, pregnancy, and customary MRI exclusions (e.g., metal implant). The primary reasons for non-completion of the neuroimaging study were unwillingness to be scanned, inability to attend the MRI study visit due to work and/or childcare, metal implants, or pregnancy. Main Outcome(s) and Measure(s)The Maltreatment and Abuse Chronology of Exposure scale was used to retrospectively assess the annual severity of exposure to ten types of CM from birth to age 18 years. Brain age was calculated from T1-weighted 3T MRI Scans using a previously published machine learning algorithm. Sensitive periods were identified using random forest regression with conditional inference trees. ResultsForty-nine (53.3%) of the 92 mothers (mean [SD] age, 32.4 [4.3] years) reported experiencing one or more types of CM. Total CM severity was associated with accelerated brain aging ({beta}=0.05, 95% CI, 0.02 to 0.09, p<.005). The most robust type/time risk factors for accelerated brain aging were parental physical abuse between ages 4 to 6 years, witnessing sibling violence between ages 4 to 15 years, parental verbal abuse between ages 10 to 12 years, and parental emotional neglect between ages 16 to 18 years. Conclusions and RelevanceSeveral types of CM between ages 4-18 years were associated with accelerated brain aging. Understanding how these specific types and ages of exposure contribute to accelerated brain aging may provide important insights into preventing key clinical consequences of CM. SUMMARYQuestion: How does childhood adversity relate to brain aging in adulthood, and are there sensitive periods for this association? Findings: In this cohort-based study of adult women, we observed sensitive periods for the association between adult brain aging and five classes of childhood maltreatment: parental physical abuse, parental verbal abuse, parental emotional neglect, and witnessing sibling violence. Meaning: These findings suggest that maltreatment subtype and age at exposure may be important factors contributing to the impact of childhood adversity on brain aging later in life.

neuroscience↗

Material-Driven Fibronectin Assembly Rescues Matrix Defects due to Mutations in Collagen IV in Fibroblasts

Basement membranes (BMs) provide structural support to tissues and influence cell signaling. Mutations in COL4A1/COL4A2, a major BM component, cause eye, kidney and cerebrovascular disease, including stroke. Common variants in these genes are risk factors for intracerebral hemorrhage in the general population. However, the contribution of the matrix to the disease mechanism(s) and its effects on the biology of cells harboring a collagen IV mutation remain poorly understood. To shed light on this, we engineered controlled microenvironments using polymer biointerfaces coated with ECM proteins laminin or fibronectin (FN), to investigate the cellular phenotype of primary fibroblasts harboring a COL4A2+/G702D mutation. FN nanonetworks assembled on poly(ethyl acrylate) (PEA) induced increased deposition and assembly of collagen IV in COL4A2+/G702D cells, which was associated with reduced ER size and enhanced levels of protein chaperones such as BIP, suggesting increased protein folding capacity of cells. FN nanonetworks on PEA also partially rescued the reduced stiffness of the deposited matrix and cells, and enhanced cell adhesion through {beta}1-mediated signaling and actin-myosin contractility, effectively rescuing some of the cellular phenotypes associated with COL4A1/4A2 mutations. Collectively, these results suggest that biomaterials are able to shape the matrix and cellular phenotype of the COL4A2+/G702D mutation in patient-derived cells.

bioengineering↗