A spatiotemporal complexity architecture of human brain activity.

The human brain operates in large-scale functional networks. These networks are an expression of temporally correlated activity across brain regions, but how global network properties relate to the neural dynamics of individual regions remains incompletely understood. Here, we show that the brain's network architecture is tightly linked to critical episodes of neural regularity, visible as spontaneous "complexity drops" in functional magnetic resonance imaging signals. These episodes closely explain functional connectivity strength between regions, subserve the propagation of neural activity patterns, and reflect interindividual differences in age and behavior. Furthermore, complexity drops define neural activity states that dynamically shape the connectivity strength, topological configuration, and hierarchy of brain networks and comprehensively explain known structure-function relationships within the brain. These findings delineate a principled complexity architecture of neural activity-a human "complexome" that underpins the brain's functional network organization.

Reduced resilience of brain state transitions in anti-N-methyl-D-aspartate receptor encephalitis.

Patients with anti-N-methyl-aspartate receptor (NMDA) receptor encephalitis suffer from a severe neuropsychiatric syndrome, yet most patients show no abnormalities in routine magnetic resonance imaging. In contrast, advanced neuroimaging studies have consistently identified disrupted functional connectivity in these patients, with recent work suggesting increased volatility of functional state dynamics. Here, we investigate these network dynamics through the spatiotemporal trajectory of meta-state transitions, yielding a time-resolved account of brain state exploration in anti-NMDA receptor encephalitis. To this end, resting-state functional magnetic resonance imaging data were acquired in 73 patients with anti-NMDA receptor encephalitis and 73 age- and sex-matched healthy controls. Time-resolved functional connectivity was clustered into brain meta-states, giving rise to a time-resolved transition network graph with states as nodes and transitions between brain meta-states as weighted, directed edges. Network topology, robustness and transition cost of these transition networks were compared between groups. Transition networks of patients showed significantly lower local efficiency (t = -2.41, pFDR  = .029), lower robustness (t = -2.01, pFDR  = .048) and higher leap size (t = 2.18, pFDR  = .037) compared with controls. Furthermore, the ratio of within-to-between module transitions and state similarity was significantly lower in patients. Importantly, alterations of brain state transitions correlated with disease severity. Together, these findings reveal systematic alterations of transition networks in patients, suggesting that anti-NMDA receptor encephalitis is characterized by reduced stability of brain state transitions and that this reduced resilience of transition networks plays a clinically relevant role in the manifestation of the disease.

Functional connectivity dynamics reflect disability and multi-domain clinical impairment in patients with relapsing-remitting multiple sclerosis.

BACKGROUND & AIM: Multiple sclerosis (MS) is an autoimmune disease of the central nervous system associated with deficits in cognitive and motor functioning. While structural brain changes such as demyelination are an early hallmark of the disease, a characteristic profile of functional brain alterations in early MS is lacking. Functional neuroimaging studies at various disease stages have revealed complex and heterogeneous patterns of aberrant functional connectivity (FC) in MS, with previous studies largely being limited to a static account of FC. Thus, it remains unclear how time-resolved FC relates to variance in clinical disability status in early MS. We here aimed to characterize brain network organization in early MS patients with time-resolved FC analysis and to explore the relationship between disability status, multi-domain clinical outcomes and altered network dynamics. METHODS: Resting-state functional MRI (rs-fMRI) data were acquired from 101 MS patients and 101 age- and sex-matched healthy controls (HC). Based on the Expanded Disability Status Score (EDSS), patients were split into two sub-groups: patients without clinical disability (EDSS ≤ 1, n = 36) and patients with mild to moderate levels of disability (EDSS ≥ 2, n = 39). Five dynamic FC states were extracted from whole-brain rs-fMRI data. Group differences in static and dynamic FC strength, across-state overall connectivity, dwell time, transition frequency, modularity, and global connectivity were assessed. Patients' impairment was quantified as custom clinical outcome z-scores (higher: worse) for the domains depressive symptoms, fatigue, motor, vision, cognition, total brain atrophy, and lesion load. Correlation analyses between functional measures and clinical outcomes were performed with Spearman partial correlation analyses controlling for age. RESULTS: Patients with mild to moderate levels of disability exhibited a more widespread spatiotemporal pattern of altered FC and spent more time in a high-connectivity, low-occurrence state compared to patients without disability and HCs. Worse symptoms in all clinical outcome domains were positively associated with EDSS scores. Furthermore, depressive symptom severity was positively related to functional dynamics as measured by state-specific global connectivity and default mode network connectivity with attention networks, while fatigue and motor impairment were related to reduced frontoparietal network connectivity with the basal ganglia. CONCLUSIONS: Despite comparably low impairment levels in early MS, we identified distinct connectivity alterations between patients with mild to moderate disability and those without disability, and these changes were sensitive to clinical outcomes in multiple domains. Furthermore, time-resolved analysis uncovered alterations in network dynamics and clinical correlations that remained undetected with conventional static analyses, showing that accounting for temporal dynamics helps disentangle the relationship between functional alterations, disability status, and symptoms in early MS.

No party, no drugs? Use of stimulants, dissociative drugs, and GHB/GBL during the early COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic is presumably having an impact on the consumption of psychoactive substances. Social distancing and lockdown measures may particularly affect the use of "party drugs" (e.g., stimulants, dissociatives, and GHB/GBL) through the absence of typical use settings. We aimed to analyse the use patterns of those substances and underlying motivations before and during the pandemic. METHODS: A subsample of 1,231 users of stimulants (amphetamine, methamphetamine, MDMA/ecstasy, cocaine), dissociative drugs (ketamine, dextromethorphan, PCP), and GHB/GBL was assessed from 30th April to 4th August 2020 as part of the Corona Drug Survey, a cross-sectional international online survey in five languages that included a total of 5,049 participants. The reported use of distinct substances and the underlying motivations were ascertained before (retrospectively) and during the pandemic. Furthermore, associations between drug use as a coping mechanism, pandemic-related stressors, and substance use were examined. RESULTS: Regarding the reported frequency of use during the pandemic, 48.0-64.8% of the sample ceased or decreased, 11.9-25.5% maintained, and 23.6-29.1% increased their consumption. MDMA/ecstasy showed the strongest decrease and GHB/GBL and dissociatives the highest increase. Participants reported that price, quality, and supply were mostly unaffected by the pandemic. The most common motivations before and during the pandemic were mood-related factors, such as a desire to feel exhilarated, euphoric, high, or buzzed. The relevance of social purposes and mood-related motivators declined during the pandemic, whereas dealing with boredom increased. Overall, 16.4-35.6% perceived drug use as helpful for dealing with pandemic-related stressors, which were associated with an increased consumption frequency. CONCLUSION: The early stage of the COVID-19 pandemic was associated with major changes in the use of "party drugs". Those who increased their level of drug use and perceived it as a coping strategy in particular might be targeted with adaptive preventive and therapeutic measures.

Cannabis use during the early COVID-19 pandemic: Use patterns, predictors, and subjective experiences.

Background: Even in the early stages, global crises such as the COVID-19 pandemic lead to serious dislocations of social life, secondary adjustment reactions to external restrictions and individual concerns. Coping mechanisms may also include dysfunctional strategies like an increase of drug use. Considering the wide-spread use of cannabis, the aim of this study was to elucidate the interplay of social restrictions, psychopathology, concerns related to the pandemic in addition to the users' experiences, motivations and consumption quantities during the early COVID-19 pandemic. It was presumed that cannabis intake would increase during the early phase of the crisis and that consumption quantities would be related to corona-related restrictions, concerns as well as subjective substance effects and psychopathology. Materials and methods: As part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages, consumption quantities and patterns of cannabis use in the early phase of the pandemic from April to August 2020 were examined. Participants retrospectively rated restrictions and concerns related to the pandemic, motives of cannabis use prior to and during 1 month the pandemic, and subjective consumption effects. Results: Cannabis use behavior showed no significant differences when consumption quantities prior and during 1 month after the COVID-19 outbreak were compared. Higher quantities of cannabis intake prior and during 1 month of the pandemic as well as more corona-related concern were associated with an increased perception of positive effects of cannabis during the pandemic. Predictors of its use during 1 month of pandemic were higher pre-pandemic consumption quantity, older age, quarantinization, a lesser degree of being affected by negative effects of the pandemic and a stronger subjective experience of corona-related positive effects of cannabis. Comparisons of the motives for cannabis intake in the pre-pandemic versus the pandemic period showed that all rationales for consumption were reported less frequently, except boredom. Conclusion: Frequencies of cannabis intake remained relatively stable in the early pandemic phase. Risk factors for increased use seem related to habitual consumption patterns that become more prominent under quarantinization. The use of cannabis as a dysfunctional coping strategy might not be amenable via self-report and should therefore receive special attention in clinical contexts.

Psychedelic Experiences During the Early COVID-19 Pandemic: Findings From an International Online Survey.

Introduction: The current corona virus disease (COVID-19) pandemic has caused a serious global health crisis that has affected large parts of the public and private life worldwide, including the use of psychoactive substances. In this study, we investigated the effect of the COVID-19 pandemic on the use of serotonergic psychedelics, i.e., the settings in which people use psychedelics, the motives of usage, and the subjective quality of psychedelic experiences. Methods: The study was part of an international, cross-sectional, internet-based survey (N = 5,049) available in five languages (English, German, Spanish, Italian, and Korean) carried out during the early phase of the pandemic from April to August 2020. Participants were asked to retrospectively rate settings and motives of psychedelic substance use before the pandemic and in the last 4 weeks during the pandemic, as well as changes in psychedelic experiences. Results: Of n = 1,375 participants that reported the use psychedelics in 2019 or 2020, n = 642 (46.6%) also took psychedelics during the pandemic. During the pandemic, participants used psychedelics significantly less often in settings that were outside their home. Top motives to use psychedelics were comparable before and during the pandemic, but participants consumed less out of curiosity, to celebrate, or because friends took it, and more out of boredom. An increase in positively connoted, often pro-social experiences was observed. Two thirds of participants who used psychedelics during the pandemic claimed that psychedelics had helped them to deal better with the corona pandemic at least slightly. Discussion: Changes in setting and motives were mostly in line with restrictions caused by control measures to contain the spread of the virus. The unexpected increase in positively connoted experiences possibly reflects a favorable interaction of environmental macro- and individual micro-contexts during the pandemic (e.g., by reducing the use in more uncontrolled recreational settings or by encouraging a strong self-selection of substance users due to the expectation of "bad trips"). Increased pro-social feelings under psychedelics might reflect a desire for social interactions in times of social distancing and pandemic-related stress and anxiety.

Predictors of Alcohol Consumption Among Younger Adults During the First Phase of the COVID-19 Pandemic.

Background: The COVID-19 pandemic may lead to negative mental health effects but the effect on alcohol consumption among younger adults is unclear. We assess predictors of change in alcohol consumption during the first phase of the COVID-19 pandemic among younger adults. Methods: This cross-sectional internet-based survey was part of an overarching project, the Corona Drug Survey, which was conducted from April 30 to August 4, 2020. Participants of any sex and ≥18 years old were included. The primary outcome measure was change in alcohol consumption during the early COVID-19 pandemic. We implemented an ordinal logistic regression to assess the effect (odds ratio [OR] and 95% confidence interval [CI]) of the following predictors: quarantine restrictions on leaving the residence, number of individuals in the household, problematic alcohol consumption before the pandemic (CAGE [cutting down, annoyance by criticism, guilty feeling, and eye-opener] score), personal concern regarding the pandemic, age, and sex. Results: 3,321 participants with a mean age of 32 (SD: 13) years were included in this study. 70.4% of participants reported less or unchanged alcohol consumption in the recent 4 weeks of the pandemic compared to before the pandemic. A higher number of individuals in the household was associated with a reduced alcohol consumption (OR = 0.869; 95% CI = 0.815-0.927). No quarantine restrictions on leaving the residence (OR = 1.593; 95% CI = 1.397-1.817), a higher age (1.006; 1.001-1.011), and female sex (compared to males: 1.206; 1.062-1.371) were associated with an increase in alcohol consumption. The CAGE score before the pandemic (OR = 0.983; 95% CI = 0.931-1.037) and the pandemic concern (0.927; 0.857-1.003) were not associated with a significant change in alcohol consumption. Celebrations were no longer frequent drinking occasions during the pandemic compared to before the pandemic. The majority of participants (60.9%) did not use alcohol drinking as a coping mechanism to mitigate negative effects of the pandemic. Interpretation: In this cohort of younger adults with fewer celebratory drinking occasions, restrictions on leaving the residence and the number of persons in the household were the strongest predictors of reduced alcohol consumption during the early phase of the pandemic.