Biology subjects

Kizhner, A.

Publications and source records attributed to Kizhner, A..

4 recordsLinked to original sources

bioRxiv2023

Longitudinal analysis of innate immune system in infants with perinatal HIV infection until 18 months of age

With the advent of antiretroviral therapy (ART), perinatal HIV infection is declining globally but prevalence in Sub-Saharan Africa is still greater than other nations. The relationship of HIV replication in early infancy and the developing immune system is not well understood. In this study, we investigated cellular components of the innate immune system including Natural Killer (NK) cells, monocytes, and Dendritic Cells (DC) in a cohort of HIV exposed infected (HEI) and age-matched HIV exposed uninfected (HEU) infants from Mozambique. Study entry was at the first visit after delivery at age 1-2 months for HIV diagnosis and initiation of ART. Phenotypic analysis by multi-parameter flow cytometry revealed an expansion of total NK cells and the dysfunctional, CD56-CD16+, NK cell subset; increased activation in monocytes and DC; and higher levels of inflammatory homing receptor CCR5 on circulating DC subsets in the HEI infants. NKG2A, an inhibitory receptor for NK cytolytic function, was reduced in HEI compared to HEU and positively correlated with pre-ART viral load (VL) while expression of CCR2, the inflammatory homing receptor, on NK was negatively correlated with VL. Other subsets exhibited positive correlations with VL including the frequency of intermediate monocytes amongst total monocytes. Longitudinal analysis of VL indicated suboptimal ART adherence in HEI. Regardless of level of viral suppression achieved, the frequencies of specific innate immune subsets in HEI were normalized to HEU by 18m. These data support the notion that in early life, NK cells play a role in virus control and should be explored for functional attributes that are effective against HIV at this time during development. Overall, our study provides high resolution overview of the innate immune system during perinatal HIV infection. Author SummaryVertical transmission of HIV has been reduced globally in recent years, however in utero exposure and acquisition of HIV continues to occur, especially in sub-Saharan Africa. Immediate ART initiation is recommended in infants diagnosed with HIV, but adherence is often suboptimal due to behavioral and sociological challenges. The impacts of perinatal HIV infection and ART on the developing immune system in infants are still unclear. Here, we evaluated a cohort of HIV exposed infected infants, and age-matched HIV exposed uninfected infants from Mozambique at pre-ART (age 1-2m) and post-ART longitudinally (up to 18m) specifically to compare the innate immune cellular components. We found that circulating innate immune cells including Natural Killer (NK) cells, monocytes, and Dendritic Cells (DC) exhibited altered distributions and more activated (inflammatory) phenotypes at pre-ART in infants with HIV suggesting the presence of a virus specific immune response. Despite suboptimal ART adherence in the cohort, differences in innate immune subsets between infected (suppressed and unsuppressed) and uninfected were not observed longitudinally pointing to normalized immune development despite HIV infection. Our study provides new insights into the early innate immune response during perinatal HIV.

immunology↗

bioRxiv2021

The Dual Mechanisms of Cognitive Control dataset: A theoretically-guided within-subject task fMRI battery

Cognitive control is a critical higher mental function, which is subject to considerable individual variation, and is impaired in a range of mental health disorders. We describe here the initial release of Dual Mechanisms of Cognitive Control (DMCC) project data, the DMCC55B dataset, with 55 healthy unrelated young adult participants. Each participant performed four well-established cognitive control tasks (AX-CPT, Cued Task-Switching, Sternberg Working Memory, and Stroop) while undergoing functional MRI scanning. The dataset includes a range of state and trait self-report questionnaires, as well as behavioural tasks assessing individual differences in cognitive ability. The DMCC project is on-going and features additional components (e.g., related participants, manipulations of cognitive control mode, resting state fMRI, longitudinal testing) that will be publicly released following study completion. This DMCC55B subset is released early with the aim of encouraging wider use and greater benefit to the scientific community. The DMCC55B dataset is suitable for benchmarking and methods exploration, as well as analyses of task performance and individual differences.

neuroscience↗

bioRxiv2020

Frontoparietal pattern similarity analyses of cognitive control in monozygotic twins

The ability to flexibly adapt thoughts and actions in a goal-directed manner appears to rely on cognitive control mechanisms that are strongly impacted by individual differences. A powerful research strategy for investigating the nature of individual variation is to study monozygotic (identical) twins. Evidence of twin effects have been observed in prior behavioral and neuroimaging studies, yet within the domain of cognitive control, it remains to be demonstrated that the neural underpinnings of such effects are specific and reliable. Here, we utilize a multi-task, within-subjects event-related neuroimaging design with functional magnetic resonance imaging to investigate twin effects through multivariate pattern similarity analyses. We focus on fronto-parietal brain regions exhibiting consistently increased activation associated with cognitive control demands across four task domains: selective attention, context processing, multi-tasking, and working memory. Healthy young adult monozygotic twin pairs exhibited increased similarity of within- and cross-task activation patterns in these fronto-parietal regions, relative to unrelated pairs. Twin activation pattern similarity effects were clearest under high control demands, were not present in a set of task-unrelated parcels or due to anatomic similarity, and were primarily observed during the within-trial timepoints in which the control demands peaked. Together, these results indicate that twin similarity in the neural representation of cognitive control may be domain-general but also functionally and temporally specific in relation to the level of control demand. The findings suggest a genetic and/or environmental basis for individual variation in cognitive control function, and highlight the potential of twin-based neuroimaging designs for exploring heritability questions within this domain.

neuroscience↗

bioRxiv2020

The Dual Mechanisms of Cognitive Control (DMCC) Project

The Dual Mechanisms of Cognitive Control (DMCC) project provides an ambitious and rigorous empirical test of a theoretical framework that posits two key cognitive control modes: proactive and reactive. The frameworks central tenets are that proactive and reactive control reflect domain-general dimensions of individual variation, with distinctive neural signatures, involving lateral prefrontal cortex (PFC) in interactions with other brain networks and circuits (e.g., frontoparietal, cingulo-opercular). In the DMCC project, each participant is scanned while performing theoretically-targeted variants of multiple well-established cognitive control tasks (Stroop, Cued Task-Switching, AX-CPT, Sternberg Working Memory) in three separate imaging sessions, that each encourage utilization of different control modes, plus also completes an extensive out-of-scanner individual differences battery. Additional key features of the project include a high spatio-temporal resolution (multiband) acquisition protocol, and a sample that includes a substantial subset of monozygotic twin pairs and participants recruited from the Human Connectome Project. Although data collection is still continuing (target N=200), we provide an overview of the study design and protocol, planned analytic approaches and methodological development, along with initial results (N=80) revealing novel evidence of a domain-general neural signature of reactive control. In the interests of scientific community building, the dataset will be made public at project completion, so it can serve as a valuable resource.

neuroscience↗