Wearing a KN95/FFP2 facemask induces subtle yet significant brain functional connectivity modifications restricted to the salience network.

BACKGROUND: The use of facemasks is one of the consequences of the coronavirus disease 2019 (COVID-19) pandemic. We used resting-state functional magnetic resonance imaging (fMRI) to search for subtle changes in brain functional connectivity, expected notably related to the high-level salience network (SN) and default mode network (DMN). METHODS: Prospective crossover design resting 3-T fMRI study with/without wearing a tight FFP2/KN95 facemask, including 23 community-dwelling male healthy controls aged 29.9 ± 6.9 years (mean ± standard deviation). Physiological parameters, respiration frequency, and heart rate were monitored. The data analysis was performed using the CONN toolbox. RESULTS: Wearing an FFP2/KN95 facemask did not impact respiration or heart rate but resulted in a significant reduction in functional connectivity between the SN as the seed region and the left middle frontal and precentral gyrus. No difference was found when the DMN, sensorimotor, visual, dorsal attention, or language networks were used as seed regions. In the absence of significant changes of physiological parameter respiration and heart rate, and in the absence of changes in lower-level functional networks, we assume that those subtle modifications are cognitive consequence of wearing facemasks. CONCLUSIONS: The effect of wearing a tight FFP2/KN95 facemask in men is limited to high-level functional networks. Using the SN as seed network, we observed subtle yet significant decreases between the SN and the left middle frontal and precentral gyrus. Our observations suggest that wearing a facemask may change the patterns of functional connectivity with the SN known to be involved in communication, social behavior, and self-awareness.

Enhanced resting-state EEG source functional connectivity within the default mode and reward-salience networks in internet gaming disorder.

BACKGROUND: The two key mechanisms affected by internet gaming disorder (IGD) are cognitive and reward processing. Despite their significance, little is known about neurophysiological features as determined using resting-state electroencephalography (EEG) source functional connectivity (FC). METHODS: We compared resting-state EEG source FC within the default mode network (DMN) and reward/salience network (RSN) between patients with IGD and healthy controls (HCs) to identify neurophysiological markers associated with cognitive and reward processing. A total of 158 young male adults (79 patients with IGD and 79 HCs) were included, and the source FC of the DMN and RSN in five spectral bands (delta, theta, alpha, beta, and gamma) were assessed. RESULTS: Patients with IGD showed increased theta, alpha, and beta connectivity within the DMN between the orbitofrontal cortex and parietal regions compared with HCs. In terms of RSN, patients with IGD exhibited elevated alpha and beta connectivity between the anterior cingulate gyrus and temporal regions compared with HCs. Furthermore, patients with IGD showed negative correlations between the severity of IGD symptoms and/or weekly gaming time and theta and alpha connectivity within the DMN and theta, alpha, and beta connectivity within the RSN. However, the duration of IGD was not associated with EEG source FC. CONCLUSIONS: Hyper-connectivities within the DMN and RSN may be considered potential state markers associated with symptom severity and gaming time in IGD.

Mindfulness-Enhanced Computerized Cognitive Training for Depression: An Integrative Review and Proposed Model Targeting the Cognitive Control and Default-Mode Networks.

Depression is often associated with co-occurring neurocognitive deficits in executive function (EF), processing speed (PS) and emotion regulation (ER), which impact treatment response. Cognitive training targeting these capacities results in improved cognitive function and mood, demonstrating the relationship between cognition and affect, and shedding light on novel targets for cognitive-focused interventions. Computerized cognitive training (CCT) is one such new intervention, with evidence suggesting it may be effective as an adjunct treatment for depression. Parallel research suggests that mindfulness training improves depression via enhanced ER and augmentation of self-referential processes. CCT and mindfulness training both act on anti-correlated neural networks involved in EF and ER that are often dysregulated in depression-the cognitive control network (CCN) and default-mode network (DMN). After practicing CCT or mindfulness, downregulation of DMN activity and upregulation of CCN activity have been observed, associated with improvements in depression and cognition. As CCT is posited to improve depression via enhanced cognitive function and mindfulness via enhanced ER ability, the combination of both forms of training into mindfulness-enhanced CCT (MCCT) may act to improve depression more rapidly. MCCT is a biologically plausible adjunct intervention and theoretical model with the potential to further elucidate and target the causal mechanisms implicated in depressive symptomatology. As the combination of CCT and mindfulness has not yet been fully explored, this is an intriguing new frontier. The aims of this integrative review article are four-fold: (1) to briefly review the current evidence supporting the efficacy of CCT and mindfulness in improving depression; (2) to discuss the interrelated neural networks involved in depression, CCT and mindfulness; (3) to present a theoretical model demonstrating how MCCT may act to target these neural mechanisms; (4) to propose and discuss future directions for MCCT research for depression.

The cognitive basis of psychosocial impact in COVID-19 pandemic. Does it encircle the default mode network of the brain? A pragmatic proposal.

Epigenetics, hypothalamic-pituitary axes, environmental and metabolic influences, and transgenerational plasticity govern social behavior. Cognitive research considers the brain's default mode network (DMN) as a central hub that integrates various cognitive and social processing domains responsible for emotion perception, empathy, theory of mind, and morality. Hence, DMN is regarded as the "social brain." Upsurge in social turmoil, social anxiety, panic, depression, post-traumatic stress, hoarding, herd behavior, substance and behavioral addictions, sexual abuse, and violence in the time of the COVID-19 pandemic are intricately related to personality traits resulting in disruptive social cognition and social behavior, conceptualized as the result of unsettling and disruption of the functional nexus of the DMN. Considering overt and conspicuous display of neuroticism during the current pandemic, its impact upon modulation of the DMN functional nexus and the DMN itself, and the potential to presage cognitive impairment in the future, the authors caution that an increase in the global burden of dementia may be one of the long-term ramifications of COVID-19. Social behavior, a functional derivative of the DMN, can strikingly affect the functional nexus of DMN and the DMN itself, in a centripetal way via the phenomenon called "Experience-Dependent Plasticity," with long-term consequences. In this review, we intend to 1) decipher the association between social cognition and social behavior with the DMN, in time of COVID-19; and to 2) discuss the prospective aftermath of disrupted social behavior during the pandemic on modulation/alteration of functional connectomes of DMN or the DMN itself in the time ahead.

Abstracts for the 260th Otago Medical School Research Society Masters/ Honours Speakers Awards

The proceedings contain 8 papers. The topics discussed include: an exploration of mental health promotion in Aotearoa New Zealand: a qualitative study;vaccination, vaccine hesitancy and COVID-19 in New Zealand, 2018-2021;infra-slow pink noise stimulation can increase default-mode network activity in individuals with early Alzheimer's disease;agmatine attenuates actin dynamic alteration and synaptic dysfunction in aged rats;estrogen receptor alpha activation stimulates the Coolidge effect but has no effect on the sexual refractory period of estrogen-deprived male rats;and dissecting the receptor signaling events responsible for the immune suppressive and immune stimulatory effects of IL-10.

Changes in the Intranetwork and Internetwork Connectivity of the Default Mode Network and Olfactory Network in Patients with COVID-19 and Olfactory Dysfunction.

Olfactory dysfunction (OD) is a common symptom in coronavirus disease 2019 (COVID-19) patients. Moreover, many neurological manifestations have been reported in these patients, suggesting central nervous system involvement. The default mode network (DMN) is closely associated with olfactory processing. In this study, we investigated the internetwork and intranetwork connectivity of the DMN and the olfactory network (ON) in 13 healthy controls and 22 patients presenting with COVID-19-related OD using independent component analysis and region of interest functional magnetic resonance imaging (fMRI) analysis. There was a significant correlation between the butanol threshold test (BTT) and the intranetwork connectivity in ON. Meanwhile, the COVID-19 patients with OD showed significantly higher intranetwork connectivity in the DMN, as well as higher internetwork connectivity between ON and DMN. However, no significant difference was found between groups in the intranetwork connectivity within ON. We postulate that higher intranetwork functional connectivities compensate for the deficits in olfactory processing and general well-being in COVID-19 patients. Nevertheless, the compensation process in the ON may not be obvious at this stage. Our results suggest that resting-state fMRI is a potentially valuable tool to evaluate neurosensory dysfunction in COVID-19 patients.

P.0729 Highlights of psychedelic history and current research on psilocybin application for treatment of depression – a comprehensive literature review

Introduction: Psychedelics have seen various labels: mystical sacrament aids, potential interrogation tools for the Cold War, agents for social change in the Hippie counter movement, a panacea for various mental disorders, and a tool to “hack” of the psyche. This has led to their reputation as both societal threat and a psychopharmacological breakthrough. After the loss of data on over 1000 clinical papers spanning 40000 study subjects in the 60′s, a 40-year hiatus, and a few very determined researchers, new insights of increasingly quality have been emerging from research on the potential benefits of the use of psilocybin in depression. We aim to review available data on psilocybin for treating depression, providing a bird's-eye view on the literature (historical and current), while reporting potential neurobiological, psychological and cognitive mechanisms involved, safety and methodological concerns (as well as recent advancements), emerging modalities of treatment, with a commentary on social and cultural movements occurring in parallel to the scientific endeavor to create regulated and scientifically approved treatments. Methods: Eligible studies will be identified through an electronic search of Medline and clinicaltrials.gov from inception to the date of submission. The search strategy will combine relevant standardized subject terms and text words for psychedelics, psilocybin, and depression, with relevant Boolean operators implemented. Only articles written in the English language will be included. Reference lists from eligible studies will be cross-checked to identify potential additional studies. For data synthesis, results and outcomes will be explored narratively, along reporting and critical analysis of relevant statistical data. Results: Psilocybin emulates serotonin, with special affinity for the 5-HT2A receptor. Neuroimaging studies suggest an attenuation of the default mode network and an overall increase in multiple brain area connectivity [1]. Current treatment models involve previous psychological profiling and preparation, followed by one to two sessions where administration of 25 mg of psilocybin under supervision and support from the researcher, a physician, and a therapist, with post-treatment integration. Since 2011, five clinical studies, evaluated psilocybin treatment efficacy on patients suffering from clinical depression [2,3,4]. Limited by small samples, variability of setting, timeline, and methodology, they combined number of 139 patients. Despite these limitations, 60% of patients reported significant symptom reduction (58-83%) providing promising preliminary evidence for further investment. A recent trial found no significant difference in antidepressant effects between psilocybin and escitalopram in a selected group of patients, further contributing to this trend of research [5]. Over 50 studies addressing effects of psilocybin in depression have been approved on clinicaltrials.gov. One of these [6] is a phase 2 multicentered clinical trial, aiming to further evaluate the safety and efficacy of psilocybin in treatment resistant depression in a variable dose range. Conclusion: Psilocybin might become a promising approach to depression. These therapies have been (re)gaining social and cultural support, with parallel “off label” use in various spiritual and psychotherapeutic settings. There is a need for the upmost rigor in designing future research. Psilocybin might emerge as an important therapeutic tool for current and upcoming global mental health challenges in a post-COVID-19 world. No conflict of interest

Submaximal Exercise Provokes Increased Activation of the Anterior Default Mode Network During the Resting State as a Biomarker of Postexertional Malaise in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Background: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by disabling fatigue and postexertional malaise. We developed a provocation paradigm with two submaximal bicycle exercise stress tests on consecutive days bracketed by magnetic resonance imaging, orthostatic intolerance, and symptom assessments before and after exercise in order to induce objective changes of exercise induced symptom exacerbation and cognitive dysfunction. Method: Blood oxygenation level dependent (BOLD) scans were performed while at rest on the preexercise and postexercise days in 34 ME/CFS and 24 control subjects. Seed regions from the FSL data library with significant BOLD signals were nodes that clustered into networks using independent component analysis. Differences in signal amplitudes between groups on pre- and post-exercise days were determined by general linear model and ANOVA. Results: The most striking exercise-induced effect in ME/CFS was the increased spontaneous activity in the medial prefrontal cortex that is the anterior node of the Default Mode Network (DMN). In contrast, this region had decreased activation for controls. Overall, controls had higher BOLD signals suggesting reduced global cerebral blood flow in ME/CFS. Conclusion: The dynamic increase in activation of the anterior DMN node after exercise may be a biomarker of postexertional malaise and symptom exacerbation in CFS. The specificity of this postexertional finding in ME/CFS can now be assessed by comparison to post-COVID fatigue, Gulf War Illness, fibromyalgia, chronic idiopathic fatigue, and fatigue in systemic medical and psychiatric diseases.

Stronger functional network connectivity and social support buffer against negative affect during the COVID-19 outbreak and after the pandemic peak.

Health and financial uncertainties, as well as enforced social distancing, during the COVID-19 pandemic have adversely affected the mental health of people. These impacts are expected to continue even after the pandemic, particularly for those who lack support from family and friends. The salience network (SN), default mode network (DMN), and frontoparietal network (FPN) function in an interconnected manner to support information processing and emotional regulation processes in stressful contexts. In this study, we examined whether functional connectivity of the SN, DMN, and FPN, measured using resting-state functional magnetic resonance imaging before the pandemic, is a neurobiological marker of negative affect (NA) during the COVID-19 pandemic and after its peak in a large sample (N = 496, 360 females); the moderating role of social support in the brain-NA association was also investigated. We found that participants reported an increase in NA during the pandemic compared to before the pandemic, and the NA did not decrease, even after the peak period. People with higher connectivity within the SN and between the SN and the other two networks reported less NA during and after the COVID-19 outbreak peak, and the buffer effect was stronger if their social support was greater. These findings suggest that the functional networks that are responsible for affective processing and executive functioning, as well as the social support from family and friends, play an important role in protecting against NA under stressful and uncontrollable situations.

SARS-CoV-2, Trait Anxiety, and the Microbiome.

During the COVID-19 pandemic, research on the relationships between the virus and its human host has become fundamental to understand this pathology and its effects. Attaining this profound understanding is critical for the effective containment and treatment of infections caused by the virus. In this review, we present some possible mechanisms by which psychopathological symptoms emerge following viral infections of the central nervous system (CNS). These proposed mechanisms are based on microbial communication and the induced priming of microglial antibody activation within the CNS through Toll-like receptor signaling. In this process, chronic microglial activation causes increased glutamate release in virally-altered, high-density neuronal structures, thereby modulating cognitive networks and information integration processes. This modulation, in turn, we suggest, affects the accuracy of sensory integration and connectivity of major control networks, such as the default mode network. The chronic activation of immunological responses and neurochemical shifts toward an elevated glutamate/gamma-aminobutyric acid ratio lead to negative reinforcement learning and suboptimal organismic functioning, for example, maintaining the body in an anxious state, which can later become internalized as trait anxiety. Therefore, we hypothesize that the homeostatic relationship between host, microbiome, and virome, would be decisive in determining the efficiency of subsequent immunological responses, disease susceptibility, and long-term psychopathological effects of diseases that impact the CNS, such as the COVID-19.

Loneliness and Neurocognitive Aging.

Loneliness imposes significant risks to physical, mental and brain health in older adulthood. With the social distancing regimes implemented during the COVID-19 pandemic, there is even greater urgency to understand the human health costs of social isolation. In this viewpoint we describe how the experience of loneliness may alter the structure and function of the human brain, and how these discoveries may guide public health policy to reduce the burden of loneliness in later life.