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Girn, M.

Publications and source records attributed to Girn, M..

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A Complexity-Science Framework for Studying Flow: Using Media to Probe Brain-Phenomenology Dynamics

Consciousness spans a range of phenomenological experiences, from effortless immersion to disengaged monotony, yet how such phenomenology emerges from brain activity is not well understood. Flow, a phenomenological experience frequently elicited by interactive media, has drawn attention for its links to performance and wellbeing, but existing neural accounts rely on single region or small network analyses that overlook the brains distributed and dynamic nature. Complexity science offers tools that capture brain-wide dynamics, but this approach has rarely been applied to flow or to its natural comparisons: boredom and frustration. Consequently, it remains unclear whether tools drawn from complexity science can objectively discriminate between these phenomenological experiences while also clarifying their neural basis. To address this uncertainty, we induced each phenomenological experience with a difficulty-titrated video game during functional magnetic resonance imaging and collected concurrent behavioral and self-report data. Our complex systems analyses revealed that flow, in this experimental setup, shows an inverse relationship to global entropy with moderate explanatory power, and is not explained by either synchronization or metastability, whereas boredom and frustration exhibit different configurations of brain-dynamics metrics. Notably, these findings integrate previously separate prefrontal and network-synchrony observations within a single dynamical systems framework and identify complexity-based markers with the potential to map the neural underpinnings of media-related benefits.

neuroscience↗

Long-term effects of psilocybin on dynamic and effectivity connectivity of fronto-striatal-thalamic circuits

Psilocybin has been shown to induce fast and sustained improvements in mental well-being across various populations, yet its long-term mechanisms of action are not fully understood. Initial evidence suggests that longitudinal functional and structural brain changes implicate fronto-striatal-thalamic (FST) circuitry, a broad system involved in goal-directed behavior and motivational states. Here, we apply empirical methods and computational modeling to resting-state fMRI data from a within-subject longitudinal psilocybin trial in psychedelic-naive healthy volunteers. We first show increases in FST dynamic activity four weeks after a full dose of psilocybin. We then proceed to mechanistically account for these increased dynamics, by showing that reduced structural constraints underlie increased FST dynamic activity post psilocybin. Further, we show that these reduced structural constraints come along with increased bottom-up and reduced top-down modulation of FST circuits. While cortical reductions in top-down modulation are linked to regional 5-HT2A receptor availability, increased information outflow via subcortical and limbic regions relate to local D2 receptor availability. Together, these findings show that increased FST flexibility weeks after psilocybin administration is linked to serotonergic-mediated decreases in top-down information flow and dopaminergic-mediated increases in bottom-up information flow. This long-term functional re-organization of FST circuits may represent a common mechanism underling the potential clinical efficacy of psilocybin across various neuropsychiatric disorders including substance abuse, major depression, and anorexia. Significance StatementFronto-striatal-thalamic systems, which underlie motivation and reward, go through profound functional and structural changes following psilocybin administration. We leveraged longitudinal fMRI data from a within-subject psilocybin trial in psychedelic-naive healthy participants to show that psilocybin increases fronto-striatal-thalamic dynamic activity as well as flexibility four weeks after dosing. Computational modeling revealed that this increased flexibility is mechanistically caused by reduced structural constraints on functional dynamics. Further long-term changes included increased bottom-up and reduced top-down information flow mediated by the serotonergic and dopaminergic systems. This long-term functional re-organization of fronto-striatal-thalamic circuits may reflect a common mechanism underlying clinical symptoms improvements across diagnostic groups, such as increased openness, improved well-being, and reductions in anhedonia, apathy, and substance craving.

neuroscience↗

Human brain changes after first psilocybin use

Psychedelics have robust effects on acute brain function and long-term behavior but whether they also cause enduring functional and anatomical brain changes is unknown. In a placebo-controlled, within-subjects, electroencephalography, and magnetic resonance imaging study in 28 healthy, entirely psychedelic-naive participants, anatomical and functional brain changes were detected from one-hour to one-month after a single high-dose (25 mg) of psilocybin. Increases in cognitive flexibility, psychological insight, and well-being were seen at one-month. Diffusion imaging done before and one-month after 25mg psilocybin revealed decreased axial diffusivity bilaterally in prefrontal-subcortical tracts that correlated with decreased brain network modularity over the same time period. Decreased modularity also correlated with improved well-being. Increased cortical signal entropy at 1- and 2-hours post-dosing predicted improved psychological well-being at one-month. Next-day psychological insight mediated the entropy to well-being relationship. All effects were exclusive to 25mg psilocybin; no effects occurred with a 1mg psilocybin placebo dose.

neuroscience↗

Functional architecture of the aging brain

The intrinsic functional organization of the brain changes into older adulthood. Age differences are observed at multiple spatial scales, from global reductions in modularity and segregation of distributed brain systems, to network-specific patterns of dedifferentiation. Whether dedifferentiation reflects an inevitable, global shift in brain function with age, circumscribed, experience dependent changes, or both, is uncertain. We employed a multi-method strategy to interrogate dedifferentiation at multiple spatial scales. Multi-echo (ME) resting-state fMRI was collected in younger (n=181) and older (n=120) healthy adults. Cortical parcellation sensitive to individual variation was implemented for precision functional mapping of each participant, while preserving group-level parcel and network labels. ME-fMRI processing and gradient mapping identified global and macroscale network differences. Multivariate functional connectivity methods tested for microscale, edge-level differences. Older adults had lower BOLD signal dimensionality, consistent with global network dedifferentiation. Gradients were largely age-invariant. Edge-level analyses revealed discrete, network-specific dedifferentiation patterns in older adults. Visual and somatosensory regions were more integrated within the functional connectome; default and frontoparietal control network regions showed greater connectivity; and the dorsal attention network was more integrated with heteromodal regions. These findings highlight the importance of multi-scale, multi-method approaches to characterize the architecture of functional brain aging.

neuroscience↗

LSD flattens the functional hierarchy of the human brain

LSD and psilocybin are serotonergic psychedelic compounds with potential in the treatment of mental health disorders. Past neuroimaging investigations have revealed that both compounds can elicit significant changes to whole-brain functional organization and dynamics. A recent proposal linked past findings into a unified model and hypothesized reduced whole-brain hierarchical organization as a key mechanism underlying the psychedelic state, but this has yet to be directly tested. We applied a non-linear dimensionality reduction technique previously used to map hierarchical connectivity gradients to pharmacological resting-state fMRI data to assess cortical organization in the LSD and psilocybin state. Results supported our primary hypothesis: The principal gradient of cortical connectivity, describing a hierarchy from unimodal to transmodal cortex, was significantly flattened under both drugs relative to their respective placebo conditions. Between-condition contrasts revealed that this was driven by a reduction of functional differentiation at both hierarchical extremes - default and frontoparietal networks at the upper end, and somatomotor at the lower. Gradient-based connectivity mapping confirmed that this was underpinned by increased unimodal-transmodal crosstalk. In addition, LSD-dependent principal gradient changes tracked changes in self-reported ego-dissolution. Results involving the second and third gradient, which respectively represent axes of sensory and executive differentiation, also showed significant alterations across both drugs. These findings provide support for a recent mechanistic model of the psychedelic state relevant to therapeutic applications of psychedelics. More fundamentally, we provide the first evidence that macroscale connectivity gradients are sensitive to a pharmacological manipulation, specifically highlighting an important relationship between cortical organization and serotonergic modulation.

neuroscience↗

Brain Network Organization During Mindful Acceptance of Emotions

Individuals use various strategies to cope with challenging emotions such as anxiety. Mindful acceptance involves broadening attentional scope and fully experiencing present moment sensory feelings (whether pleasant or unpleasant) without judgment or elaboration. In contrast, narrative-evaluation involves focusing on a narrow band of sensory experience and generating an elaborate narrative about the meaning and desirability of ones emotional feelings. The current study examined brain network organization during these strategies using graph theoretic analyses. We used a naturalistic task paradigm in which participants reflected on an anxiety-provoking issue from their personal lives and adopted each strategy in different blocks. Compared to narrative-evaluation, mindful acceptance was associated with: (i) increased global network connectivity; (ii) greater integration of interoceptive regions (mid and posterior insula) into large-scale networks; (iii) reorganization of motivational circuits including a shift in the striatums network assignment from the default network to the salience network; and (iv) a shift from default network to frontoparietal control network (FPCN) regions as central hubs that coordinate information flow. Functional connectivity patterns within the left FPCN were associated with acceptance reports. Thus, broadening attentional scope during mindful acceptance is supported by a more globally interconnected neural landscape, as well as greater information flow through FPCN regions that underlie metacognitive awareness and cognitive control.

neuroscience↗

Targeting age-related differences in brain and cognition with multimodal imaging and connectome topography profiling

I.AO_SCPLOWBSTRACTC_SCPLOWAging is characterised by accumulation of structural and metabolic changes in the brain. Recent studies suggest transmodal brain networks are especially sensitive to aging, which, we hypothesise, may be due to their apical position in the cortical hierarchy. Studying an open-access healthy cohort (n=102, age range = 30-89 years) with MRI and A{beta} PET data, we estimated age-related cortical thinning, hippocampal atrophy and A{beta} deposition. In addition to carrying out surface-based morphological and metabolic mapping, we stratified effects along neocortical and hippocampal resting-state functional connectome gradients derived from independent datasets. The cortical gradient depicts an axis of functional differentiation from sensory-motor regions to transmodal regions, whereas the hippocampal gradient recapitulates its long-axis. While age-related thinning and increased A{beta} deposition occurred across the entire cortical topography, increased A{beta} deposition was especially pronounced towards higher-order transmodal regions. Age-related atrophy was greater towards the posterior end of the hippocampal long-axis. No significant effect of age on A{beta} deposition in the hippocampus was observed. Imaging markers correlated with behavioural measures of fluid intelligence and episodic memory in a topography-specific manner. Our results strengthen existing evidence of structural and metabolic change in the aging brain and support the use of connectivity gradients as a compact framework to analyse and conceptualize brain-based biomarkers of aging.

neuroscience↗