Biology subjects

Lacadie, C.

Publications and source records attributed to Lacadie, C..

4 recordsLinked to original sources

bioRxiv2023

Ketamine Effects on Energy Metabolism, Functional Connectivity and Working Memory in Healthy Humans

Working memory (WM) is a crucial resource for temporary memory storage and the guiding of ongoing behavior. N-methyl-D-aspartate glutamate receptors (NMDARs) are thought to support the neural underpinnings of WM. Ketamine is an NMDAR antagonist that has cognitive and behavioral effects at subanesthetic doses. To shed light on subanesthetic ketamine effects on brain function, we employed a multimodal imaging design, combining gas-free calibrated functional magnetic resonance imaging (fMRI) measurement of oxidative metabolism (CMRO2), resting-state cortical functional connectivity assessed with fMRI, and WM-related fMRI. Healthy subjects participated in two scan sessions in a randomized, double-blind, placebo-controlled design. Ketamine increased CMRO2 and cerebral blood flow (CBF) in prefrontal cortex (PFC) and other cortical regions. However, resting-state cortical functional connectivity was not affected. Ketamine did not alter CBF-CMRO2 coupling brain-wide. Higher levels of basal CMRO2 were associated with lower task-related PFC activation and WM accuracy impairment under both saline and ketamine conditions. These observations suggest that CMRO2 and resting-state functional connectivity index distinct dimensions of neural activity. Ketamines impairment of WM-related neural activity and performance appears to be related to its ability to produce cortical metabolic activation. This work illustrates the utility of direct measurement of CMRO2 via calibrated fMRI in studies of drugs that potentially affect neurovascular and neurometabolic coupling.

neuroscience↗

bioRxiv2022

Developmental trajectories of the default mode, executive control, and salience networks from the third trimester through the newborn period

Social cognition is critical to early learning. Functional imaging studies in adults and older children suggest the involvement of the default mode (DMN), executive control (ECN), and salience (SAL) networks in social cognition. These networks are vulnerable to environmental insults, and abnormalities of intra- and inter-network connectivity of the three are emerging as biomarkers of neurobehavioral disorders. However, the developmental trajectories of the DMN, ECN, and SAL across the third trimester of gestation and perinatal transition remain largely unknown. Employing resting-state functional MRI studies at 30-32, 34-36, and 40-44 weeks postmenstrual age (PMA), we tested the hypothesis that both intra- and inter-network functional connectivity in the DMN, ECN, and SAL develop across the 30-46 weeks PMA time interval in a longitudinal/cross-sectional sample of 84 fetuses and neonates. A secondary analysis addressed the impact of maternal mental health assessed at 28 weeks PMA on tri-network development from 30-46 weeks PMA. The DMN, ECN, and SAL develop across the third trimester of gestation and the first postnatal month. At the intra-network level, significant increases occurred between 36 to 44 weeks PMA for all three, with network strength values significantly different from 0 beginning at 40 weeks PMA for all. Functional connectivity increased less rapidly in the DMN than in the ECN and SAL networks, suggesting slower maturation of the network subserving social interactions. In contrast, significant inter-network DMN - ECN connectivity greater than 0 was found from 36 weeks PMA through the first postnatal month, suggesting the emergence of inter-network functional connectivity in the fetal brain. Finally, higher maternal mental health symptoms measured at the beginning of the third trimester negatively affected the developmental trajectory of the SAL network across the critical time interval of 30 weeks to 44 weeks PMA. Together, these data provide a framework to compare fetuses and neonates at risk for neurobehavioral disorders and assess the impact of the environment on the developing brain.

neuroscience↗

bioRxiv2022

Sex differences in default mode network connectivity in healthy aging adults

Women show an increased lifetime risk of Alzheimers disease (AD) compared to men. Characteristic brain connectivity changes, particularly within the default mode network (DMN), have been associated with both symptomatic and preclinical AD, but the impact of sex on DMN function throughout aging is poorly understood. We investigated sex differences in DMN connectivity over the lifespan in 595 cognitively healthy participants from the Human Connectome Project - Aging cohort. We used the intrinsic connectivity distribution (a robust voxel-based metric of functional connectivity) and a seed connectivity approach to determine sex differences within the DMN and between the DMN and whole brain. Compared with men, women demonstrated increased connectivity with age in posterior DMN nodes and decreased connectivity in the medial prefrontal cortex. Differences were most prominent in the decades surrounding menopause. Seed-based analysis revealed increased connectivity in women from the posterior cingulate to angular gyrus and parahippocampal gyrus, which correlated with neuropsychological measures of declarative memory. Taken together, we show significant sex differences in DMN subnetworks over the lifespan, including patterns in aging women that resemble changes previously seen in preclinical AD. These findings highlight the importance of considering sex in neuroimaging studies of aging and neurodegeneration.

neuroscience↗

bioRxiv2022

Hypoconnectivity between anterior insula and amygdala in neonates with familial history of autism

BackgroundAltered resting state functional connectivity (FC) involving the anterior insula (aINS), a key node in the salience network, has been reported consistently in autism. MethodHere we examined, for the first time, FC between the aINS and the whole brain in a sample of full-term, postmenstrual age (PMA) matched neonates (mean 44.0 weeks, SD=1.5) who due to family history have high likelihood (HL) for developing autism (n=12) and in controls (n=41) without family history of autism (low likelihood, LL). Behaviors associated with autism were evaluated between 12 and 18 months (M=17.3 months, SD=2.5) in a subsample (25/53) of participants using the First Year Inventory (FYI). ResultsCompared to LL controls, HL neonates showed hypoconnectivity between left aINS and left amygdala. Lower connectivity between the two nodes was associated with higher FYI risk scores in the social domain (r(25) = -.561, p=.003) and this association remained robust when maternal mental health factors were considered. Considering that a subsample of LL participants (n=14/41) underwent brain imaging during the fetal period at PMA 31 and 34 weeks, in an exploratory analysis, we evaluated prospectively development of the LaINS-Lamy connectivity and found that the two areas strongly coactivate throughout the third trimester of pregnancy. ConclusionsThe study identifies left lateralized anterior insula - amygdala connectivity as a potential target of further investigation into neural circuitry that enhances likelihood of future onset of social behaviors associated with autism during neonatal and potentially prenatal periods.

neuroscience↗