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Sawicka, G.

Publications and source records attributed to Sawicka, G..

3 recordsLinked to original sources

Neurite Complexity and Plasticity Markers Track Synaptic Vesicle Density in the Living Human Brain: A Multimodal PET-MRI-EEG Study

Neuroplasticity, the brain's capacity to reorganise its structure and function, is a transdiagnostic feature across psychiatric and neurodegenerative diseases and a putative mechanism of action for pharmacological interventions. [11C]-UCBJ positron emission tomography (PET), which quantifies synaptic vesicle glycoprotein 2A (SV2A) density, offers the most direct in vivo measure of human synaptic density, but its relationship to complementary, more scalable neuroimaging measures of structural and functional plasticity remains uncharacterised. We combined [11C]-UCBJ PET, diffusion weighted imaging (DWI/NODDI), resting-state functional magnetic resonance imaging (rs-fMRI), and electroencephalography (EEG)-based sensory tasks (roving mismatch negativity, MMN; visual long-term potentiation, vLTP) in 18 healthy volunteers to test the relationship between synaptic terminal SV2A density and complementary structural and functional neuroplasticity measures, and whether these relationships were reproducible following pharmacological challenge with ketamine (n = 11) or N,N-dimethyltryptamine (DMT; n = 7). There were no statistically significant differences in PET-derived SV2A binding potential (BPND), DWI-derived neurite orientation dispersion (ODI) and structural weighted degree (SWD), EEG-derived MMN repetition suppression, and late-phase vLTP P2 potentiation, 1 to 8 days following DMT and ketamine exposure compared to baseline. BPND was coupled with ODI across cortical regions before and after pharmacological challenge, and this relationship was tighter within visual, attentional, and frontoparietal control brain networks. SWD showed a weaker, more spatially restricted association with BPND, primarily in regions belonging to the limbic and visual brain networks, but was not replicated post-drug. No consistent association was found between BPND and functional weighted degree (FWD), derived from rs-fMRI, at baseline or after pharmacological challenge. Frontotemporal BPND was positively associated with MMN repetition suppression (r = 0.61), and occipital BPND with late-phase vLTP P2 potentiation (r = 0.54), with the MMN-BPND association replicating after pharmacological challenge (r = 0.49). These findings link synaptic terminal SV2A density in the living human brain to neurite architecture and the capacity for short-term and Hebbian-like long-term synaptic plasticity, while dissociating these relationships from generic functional connectivity and magnitude of sensory-evoked responses. These data provide cross-modal validation for DWI- and EEG-derived measures as biological indices and surrogate measures of human synaptic plasticity.

neuroscience↗

Spiral brain dynamics track the temporal unfolding of subjective intensity during the N,N-dimethyltryptamine experience

Psychedelic compounds such as N,N-dimethyltryptamine (DMT) induce rapid and profound changes in conscious experience, requiring neuroimaging measures that capture how brain dynamics evolve across space and time. Emerging evidence suggests that rotational (vortex-like) dynamics may contribute to the coordination of large-scale neural activity. Here, we introduce two vorticity-based metrics; spiral vorticity (SV) and spatial spiral vorticity dispersion (SSVD), to quantify the rotational organization and spatial heterogeneity of large-scale cortical phase dynamics. Using fMRI data acquired under placebo and DMT in a within-subject design, we assessed these measures globally, across resting-state networks, and regionally to examine their relationship to subjective intensity. DMT increased SV and SSVD and reduced temporal irreversibility, indicating stronger rotational organization, greater spatial heterogeneity, and altered directional structure of cortical dynamics. Effects were non-uniform across functional systems, with the largest changes in default mode, visual, frontoparietal, and dorsal attention networks. Both vorticity measures tracked the temporal evolution of subjective intensity globally, while network-level analyses revealed spatially heterogeneous brain-experience coupling. Spatiotemporally resolved analyses further showed that the strongest reorganization of spiral dynamics emerged during offset and recovery rather than at peak subjective intensity. These findings identify spiral dynamics as a time-resolved neural signature of the DMT experience. By quantifying the rotational structure and spatial heterogeneity of cortical phase flow, vorticity-based measures provide a framework for linking large-scale brain dynamics to evolving subjective experience.

neuroscience↗

Detecting neuroplastic effects induced by ketamine in healthy human subjects: a multimodal approach

We investigated ketamines neuroplastic effects in healthy human subjects using integrated Positron Emission Tomography (PET)/Magnetic Resonance Imaging (MRI) measures before and 1-8 days after a single psychedelic dose of ketamine (1 mg/kg, intravenous). Eleven participants underwent two PET/MRI scans with [11C]-UCBJ (synaptic density/plasticity), 1H-MRS (Glutamate and GABA), and resting-state fMRI (intrinsic brain activity, functional connectivity, graph-theoretic metrics), before and after ketamine. While group-level analyses showed only trend-level increases in PET synaptic markers, we observed significantly elevated Anterior Cingulate Cortex (ACC) glutamate levels post-ketamine. Functional connectivity analyses revealed decreased within-network integrity, particularly in high-order networks like the default mode network (DMN), alongside increased low-to-high-order network integration. Our multimodal analysis showed that increased [11C]-UCBJ volume distribution (VT), a putative index of synaptic plasticity, correlated with reduced intrinsic activity in DMN regions and decreased influence of the posterior cingulate cortex (PCC) in global network dynamics. By linking molecular and network-level changes, our results point to the PCC as a central hub where ketamine may reshape brain hierarchies in the long term, providing new directions for understanding its therapeutic mechanisms and developing targeted treatments.

neuroscience↗