Biology subjects

Giampietro, V.

Publications and source records attributed to Giampietro, V..

3 recordsLinked to original sources

bioRxiv2021

Epigenetic mediation of AKT1 rs1130233 s effect on delta-9-tetrahydrocannabinol-induced medial temporal function during fear processing

High doses of delta-9-tetrahydrocannabinol (THC), the main psychoactive component of cannabis, have been shown to have anxiogenic effects. Also, THC effects have been shown to be modulated by genotype, including the single nucleotide polymorphism (SNP) rs1130233 at the protein kinase AKT1 gene, a key component of the dopamine signaling cascade. As such, it is likely that epigenetic methylation around this SNP may affect AKT gene expression, which may in turn impact on the acute effects of THC on brain function. We investigated the genetic (AKT1 rs1130233) and epigenetic modulation of brain function during fear processing in a 2-session, double-blind, cross-over, randomized placebo-controlled THC administration, in 36 healthy males. Fear processing was assessed using an emotion (fear processing) paradigm, under functional magnetic resonance imaging (fMRI). Complete genetic and fMRI data was available for 34 participants. THC caused an increase in anxiety and transient psychotomimetic symptoms and para-hippocampal gyrus/ amygdala activation. Number of A alleles at the AKT1 rs1130233 SNP, and percentage methylation at the CpG11-12 site, were independently associated with a greater effect of THC on activation in a network of brain regions including left and right parahippocampal gyri, respectively. AKT1 rs1130233 moderation of the THC effect on left parahippocampal activation persisted after covarying for methylation percentage, and was partially mediated in sections of the left parahippocampal gyrus/ hippocampus by methylation percentage. These results may offer an example of how genetic and epigenetic variations influence the psychotomimetic and neurofunctional effects of THC.

neuroscience↗

bioRxiv2021

Rapid processing and quantitative evaluation of multicontrast EPImix scans for adaptive multimodal imaging

Current neuroimaging acquisition and processing approaches tend to be optimised for quality rather than speed. However, rapid acquisition and processing of neuroimaging data can lead to novel neuroimaging paradigms, such as adaptive acquisition, where rapidly processed data is used to inform subsequent image acquisition steps. Here we first evaluate the impact of several processing steps on the processing time and quality of registration of manually labelled T1-weighted MRI scans. Subsequently, we apply the selected rapid processing pipeline both to rapidly acquired multicontrast EPImix scans of 95 participants (which include T1-FLAIR, T2, T2*, T2-FLAIR, DWI & ADC contrasts, acquired in [~]1 minute), as well as to slower, more standard single-contrast T1-weighted scans of a subset of 66 participants. We quantify the correspondence between EPImix and single-contrast T1-weighted scans, using correlations between voxels and regions of interest across participants, measures of within- and between-participant identifiability as well as regional structural covariance networks. Furthermore, we explore the use of EPImix for the rapid construction of morphometric similarity networks. Finally, we quantify the reliability of EPImix-derived data using test-retest scans of 10 participants. Our results demonstrate that quantitative information can be derived from a neuroimaging scan acquired and processed within minutes, which could further be used to implement adaptive multimodal imaging and tailor neuroimaging examinations to individual patients. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=77 SRC="FIGDIR/small/430956v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@3ae0e9org.highwire.dtl.DTLVardef@1840d39org.highwire.dtl.DTLVardef@80339borg.highwire.dtl.DTLVardef@bc16cf_HPS_FORMAT_FIGEXP M_FIG Graphical abstract. C_FIG

neuroscience↗

bioRxiv2019

The heterogeneous functional architecture of the posteromedial cortex is associated with selective functional connectivity differences in Alzheimer’s disease

The posteromedial cortex (PMC) is a key region involved in the development and progression of Alzheimers disease (AD). Previous studies have demonstrated a heterogenous functional architecture of the region, with different subdivisions reflecting distinct connectivity profiles. However, little is understood about PMC functional connectivity and its differential vulnerability to AD pathogenesis. Using a data-driven approach, we applied a constrained independent component analysis (ICA) on healthy adults from the Human Connectome Project (HCP) to characterise the distinct functional subdivisions and unique functional-anatomic connectivity patterns of the PMC. These connectivity profiles were subsequently quantified in the Alzheimers Disease Neuroimaging Initiative (ADNI) study, to examine functional connectivity differences in (1) AD patients and cognitively normal (CN) participants and (2) the entire AD pathological spectrum, ranging from CN participants and participants with subjective memory complaints (SMC), through to those with mild cognitive impairment (MCI), and finally, patients diagnosed with AD. Our findings revealed decreased functional connectivity in the anterior precuneus, dorsal posterior cingulate cortex, and the central precuneus in AD patients compared to CN participants. Functional abnormalities in these subdivisions were also related to high amyloid burden and lower hippocampal volumes. Across the entire AD spectrum, functional connectivity of the central precuneus was associated with disease progression and specific deficits in memory and executive function. These findings provide new evidence showing that specific vulnerabilities in PMC functional connectivity are associated with large-scale network disruptions in AD and that these patterns may be useful for elucidating potential biomarkers for measuring disease progression in future work.

neuroscience↗