Imbalanced brain connectome: A possible link behind functional somatic disorders, multiple chemical sensitivity, and long COVID patients

Background: Functional Somatic Disorders (FSDs) are characterized by persistent physical symptoms that cannot be explained by other somatic or psychiatric conditions. Multiple Chemical Sensitivity (MCS) is a non-allergic FSD characterized by odour intolerance and various somatic symptoms being attributed to the influence of toxic environmental chemicals in low, usually harmless doses. The pathophysiology of FSDs are still not clear. Smell and taste complaints were also among the notable symptoms characterizing the covid epidemic and the latest evidence suggests overlaps between long COVID and FSDs. Method(s): The study includes advanced analysis of MRI-derived functional and structural connectomes acquired on a 3 T MR scanner. Furthermore, it includes questionnaires and paraclinical tests, e.g. the Sniffin' Stick olfactory test, Mini-Mental State Examination, and Sino-Nasal Outcome test 22. The pilot part of the project included 6 MCS patients who were compared with 6 matched healthy participants. Later follow-up included analysis of 8 multiorgan FSD and 4 post-COVID patients. Result(s): The MCS group showed important brain structural connectivity differences in 34 tracts. Notably, for MCS patients, the olfactory cortex (especially in the right hemisphere) showed decreased connectivity with regions in the emotional system. Conclusion(s): We plan to extend these findings with whole-brain modelling of the functional connectivity in the patient groups. Long-term this could be used as a 'fingerprint' which could help with diagnosis and treatment monitoring in FSDs as well as with new diagnoses such as long-COVID.Copyright © 2023

Associations between mother's depressive symptoms during pregnancy and newborn's brain functional connectivity.

Depression during pregnancy is common and the prevalence further increased during the COVID pandemic. Recent findings have shown potential impact of antenatal depression on children's neurodevelopment and behavior, but the underlying mechanisms are unclear. Nor is it clear whether mild depressive symptoms among pregnant women would impact the developing brain. In this study, 40 healthy pregnant women had their depressive symptoms evaluated by the Beck Depression Inventory-II at ~12, ~24, and ~36 weeks of pregnancy, and their healthy full-term newborns underwent a brain MRI without sedation including resting-state fMRI for evaluation of functional connectivity development. The relationships between functional connectivities and maternal Beck Depression Inventory-II scores were evaluated by Spearman's rank partial correlation tests using appropriate multiple comparison correction with newborn's gender and gestational age at birth controlled. Significant negative correlations were identified between neonatal brain functional connectivity and mother's Beck Depression Inventory-II scores in the third trimester, but not in the first or second trimester. Higher depressive symptoms during the third trimester of pregnancy were associated with lower neonatal brain functional connectivity in the frontal lobe and between frontal/temporal lobe and occipital lobe, indicating a potential impact of maternal depressive symptoms on offspring brain development, even in the absence of clinical depression.

Adolescent functional network connectivity prospectively predicts adult anxiety symptoms related to perceived COVID-19 economic adversity.

BACKGROUND: Stressful events, such as the COVID-19 pandemic, are major contributors to anxiety and depression, but only a subset of individuals develop psychopathology. In a population-based sample (N = 174) with a high representation of marginalized individuals, this study examined adolescent functional network connectivity as a marker of susceptibility to anxiety and depression in the context of adverse experiences. METHODS: Data-driven network-based subgroups were identified using an unsupervised community detection algorithm within functional neural connectivity. Neuroimaging data collected during emotion processing (age 15) were extracted from a priori regions of interest linked to anxiety and depression. Symptoms were self-reported at ages 15, 17, and 21 (during COVID-19). During COVID-19, participants reported on pandemic-related economic adversity. Differences across subgroup networks were first examined, then subgroup membership and subgroup-adversity interaction were tested to predict change in symptoms over time. RESULTS: Two subgroups were identified: Subgroup A, characterized by relatively greater neural network variation (i.e., heterogeneity) and density with more connections involving the amygdala, subgenual cingulate, and ventral striatum; and the more homogenous Subgroup B, with more connections involving the insula and dorsal anterior cingulate. Accounting for initial symptoms, subgroup A individuals had greater increases in symptoms across time (ß = .138, p = .042), and this result remained after adjusting for additional covariates (ß = .194, p = .023). Furthermore, there was a subgroup-adversity interaction: compared with Subgroup B, Subgroup A reported greater anxiety during the pandemic in response to reported economic adversity (ß = .307, p = .006), and this remained after accounting for initial symptoms and many covariates (ß = .237, p = .021). CONCLUSIONS: A subgrouping algorithm identified young adults who were susceptible to adversity using their personalized functional network profiles derived from a priori brain regions. These results highlight potential prospective neural signatures involving heterogeneous emotion networks that predict individuals at the greatest risk for anxiety when experiencing adverse events.

Multimodal neuroimaging in post-COVID syndrome and correlation with cognition.

Brain changes have been reported in the first weeks after SARS-CoV-2 infection. However, limited literature exists about brain alterations in post-COVID syndrome, a condition increasingly associated with cognitive impairment. The present study aimed to evaluate brain functional and structural alterations in patients with post-COVID syndrome, and assess whether these brain alterations were related to cognitive dysfunction. Eighty-six patients with post-COVID syndrome and 36 healthy controls were recruited and underwent neuroimaging acquisition and a comprehensive neuropsychological assessment. Cognitive and neuroimaging examinations were performed 11 months after the first symptoms of SARS-CoV-2. Whole-brain functional connectivity analysis was performed. Voxel-based morphometry was performed to evaluate grey matter volume, and diffusion tensor imaging was carried out to analyse white matter alterations. Correlations between cognition and brain changes were conducted and Bonferroni corrected. Post-COVID syndrome patients presented with functional connectivity changes, characterized by hypoconnectivity between left and right parahippocampal areas, and between bilateral orbitofrontal and cerebellar areas compared to controls. These alterations were accompanied by reduced grey matter volume in cortical, limbic and cerebellar areas, and alterations in white matter axial and mean diffusivity. Grey matter volume loss showed significant associations with cognitive dysfunction. These cognitive and brain alterations were more pronounced in hospitalized patients compared to non-hospitalized patients. No associations with vaccination status were found. The present study shows persistent structural and functional brain abnormalities 11 months after the acute infection. These changes are associated with cognitive dysfunction and contribute to a better understanding of the pathophysiology of the post-COVID syndrome.

Effects of post-acute COVID-19 syndrome on the functional brain networks of non-hospitalized individuals.

Introduction: The long-term impact of COVID-19 on brain function remains poorly understood, despite growing concern surrounding post-acute COVID-19 syndrome (PACS). The goal of this cross-sectional, observational study was to determine whether there are significant alterations in resting brain function among non-hospitalized individuals with PACS, compared to symptomatic individuals with non-COVID infection. Methods: Data were collected for 51 individuals who tested positive for COVID-19 (mean age 41±12 yrs., 34 female) and 15 controls who had cold and flu-like symptoms but tested negative for COVID-19 (mean age 41±14 yrs., 9 female), with both groups assessed an average of 4-5 months after COVID testing. None of the participants had prior neurologic, psychiatric, or cardiovascular illness. Resting brain function was assessed via functional magnetic resonance imaging (fMRI), and self-reported symptoms were recorded. Results: Individuals with COVID-19 had lower temporal and subcortical functional connectivity relative to controls. A greater number of ongoing post-COVID symptoms was also associated with altered functional connectivity between temporal, parietal, occipital and subcortical regions. Discussion: These results provide preliminary evidence that patterns of functional connectivity distinguish PACS from non-COVID infection and correlate with the severity of clinical outcome, providing novel insights into this highly prevalent disorder.

Clinical experience with the alpha2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in "Long-COVID19"

Background: Prolonged cognitive deficits ("brain fog") following COVID19 infection (long-COVID) are common and debilitating, yet there are currently no approved treatments. Cognitive impairment particularly targets the working memory and executive functions of the prefrontal cortex (PFC). The PFC has unusual neurotransmission and neuromodulation that render it vulnerable to stressors, and basic research has identified mechanisms that protect PFC connections. Based on the basic neuroscience data, we tried a combined open label treatment to bolster prefrontal function: the alpha2A-adrenoceptor agonist, guanfacine, which strengthens prefrontal connectivity, and the anti-oxidant, N- acetylcysteine (NAC), which protects mitochondria and reduces kynurenic acid blockade of NMDA receptors. Case report: Twelve patients with "brain fog" including difficulties in executive functions were treated with guanfacine (1mg, PO bedtime for the first month, increased to 2mg after 1 month, if well-tolerated) and 600 mg NAC daily. Guanfacine+NAC improved cognitive abilities in eight of the twelve patients;four patients discontinued therapy, two for unspecified reasons and two due to hypotension and/or dizziness, common side effects of guanfacine. Those who stayed on guanfacine+NAC reported improved working memory, concentration, and executive functions, including a resumption of normal workloads. One patient briefly stopped taking guanfacine due to a hypotensive episode and reported a return of cognitive deficits that abated with resumed guanfacine treatment. Conclusion(s): Although placebo-controlled trials will be needed to more rigorously demonstrate efficacy, as these agents have established safety, they may be immediately helpful in treating the large number of patients suffering from prolonged cognitive deficits following COVID19 infection.Copyright © 2022 The Author(s)

Brain Networks Associated With COVID-19 Risk: Data From 3662 Participants.

BACKGROUND: Our behavioral traits, and subsequent actions, could affect the risk of exposure to the coronavirus disease of 2019 (COVID-19). The current study aimed to determine whether unique brain networks are associated with the COVID-19 infection risk. METHODS: This research was conducted using the UK Biobank Resource. Functional magnetic resonance imaging scans in a cohort of general population (n = 3662) were used to compute the whole-brain functional connectomes. A network-informed machine learning approach was used to identify connectome and nodal fingerprints that are associated with positive COVID-19 status during the pandemic up to February fourth, 2021. RESULTS: The predictive models successfully identified 6 fingerprints that were associated with COVID-19 positive, compared to negative status (all p values < 0.005). Overall, lower integration across the brain modules and increased segregation, as reflected by internal within module connectivity, were associated with higher infection rates. More specifically, COVID-19 positive status was associated with 1) reduced connectivity between the central executive and ventral salience, as well as between the dorsal salience and default mode networks; 2) increased internal connectivity within the default mode, ventral salience, subcortical and sensorimotor networks; and 3) increased connectivity between the ventral salience, subcortical and sensorimotor networks. CONCLUSION: Individuals are at increased risk of COVID-19 infections if their brain connectome is consistent with reduced connectivity in the top-down attention and executive networks, along with increased internal connectivity in the introspective and instinctive networks. These identified risk networks could be investigated as target for treatment of illnesses with impulse control deficits.

Amygdala connectivity related to subsequent stress responses during the COVID-19 outbreak.

Introduction: The amygdala plays an important role in stress responses and stress-related psychiatric disorders. It is possible that amygdala connectivity may be a neurobiological vulnerability marker for stress responses or stress-related psychiatric disorders and will be useful to precisely identify the vulnerable individuals before stress happens. However, little is known about the relationship between amygdala connectivity and subsequent stress responses. The current study investigated whether amygdala connectivity measured before experiencing stress is a predisposing neural feature of subsequent stress responses while individuals face an emergent and unexpected event like the COVID-19 outbreak. Methods: Data collected before the COVID-19 pandemic from an established fMRI cohort who lived in the pandemic center in China (Hubei) during the COVID-19 outbreak were used to investigate the relationship between amygdala connectivity and stress responses during and after the pandemic in 2020. The amygdala connectivity was measured with resting-state functional connectivity (rsFC) and effective connectivity. Results: We found the rsFC of the right amygdala with the dorsomedial prefrontal cortex (dmPFC) was negatively correlated with the stress responses at the first survey during the COVID-19 outbreak, and the rsFC between the right amygdala and bilateral superior frontal gyri (partially overlapped with the dmPFC) was correlated with SBSC at the second survey. Dynamic causal modeling suggested that the self-connection of the right amygdala was negatively correlated with stress responses during the pandemic. Discussion: Our findings expand our understanding about the role of amygdala in stress responses and stress-related psychiatric disorders and suggest that amygdala connectivity is a predisposing neural feature of subsequent stress responses.

Network segregation in aging females and evaluation of the impact of sex steroid hormones.

Males and females show differential patterns in connectivity in resting-state networks (RSNs) during normal aging, from early adulthood to late middle age. Age-related differences in network integration (effectiveness of specialized communication at the global network level) and segregation (functional specialization at the local level of specific brain regions) may also differ by sex. These differences may be due at least in part to endogenous hormonal fluctuation, such as that which occurs in females during midlife with the transition to menopause when levels of estrogens and progesterone drop markedly. A limited number of studies that have investigated sex differences in the action of steroid hormones in brain networks. Here we investigated how sex steroid hormones relate to age-network relationships in both males and females, with a focus on network segregation. Females displayed a significant quadratic relationship between age and network segregation for the cerebellar-basal ganglia and salience networks. In both cases, segregation was still increasing through adulthood, highest in midlife, and with a downturn thereafter. However, there were no significant relationships between sex steroid hormone levels and network segregation levels in females, and they did not exhibit significant associations between progesterone or 17ß-estradiol and network segregation. Patterns of connectivity between the cerebellum and basal ganglia have been associated with cognitive performance and self-reported balance confidence in older adults. Together, these findings suggest that network segregation patterns with age in females vary by network, and that sex steroid hormones are not associated with this measure of connectivity in this cross-sectional analysis. Though this is a null effect, it remains critical for understanding the extent to which hormones relate to brain network architecture.

Brain disorders: Impact of mild SARS-CoV-2 may shrink several parts of the brain.

Coronavirus (COVID-19) is a highly infectious respiratory infection discovered in Wuhan, China, in December 2019. As a result of the pandemic, several individuals have experienced life-threatening diseases, the loss of loved ones, lockdowns, isolation, an increase in unemployment, and household conflict. Moreover, COVID-19 may cause direct brain injury via encephalopathy. The long-term impacts of this virus on mental health and brain function need to be analysed by researchers in the coming years. This article aims to describe the prolonged neurological clinical consequences related to brain changes in people with mild COVID-19 infection. When compared to a control group, people those who tested positive for COVID-19 had more brain shrinkage, grey matter shrinkage, and tissue damage. The damage occurs predominantly in areas of the brain that are associated with odour, ambiguity, strokes, reduced attention, headaches, sensory abnormalities, depression, and mental abilities for few months after the first infection. Therefore, in patients after a severe clinical condition of COVID-19, a deepening of persistent neurological signs is necessary.

Reduced brain activity and functional connectivity during creative idea generation in individuals with smartphone addiction.

Since the COVID-19 outbreak, the frequency of smartphone use has surged, which has caused an increase in smartphone addiction among individuals. Smartphone addiction can impair various cognitive abilities. However, to date, the impact of smartphone addiction on creative cognition remains unclear. The current functional near-infrared spectroscopy (fNIRS) study compared neural differences between smartphone addiction tendency (SAT) and healthy control (HC) individuals during creative idea generation. In particular, by manipulating a key component of creative cognition, that is, overcoming semantic constraints, we explored whether SAT individuals could overcome semantic constraints. Both the SAT and HC groups completed the alternate uses task (AUT) in semantic constraint and unconstraint conditions. The results indicated that the prefrontal cortex (PFC) and temporal region were less active during AUT in the SAT group than in the HC group. In the SAT group, the PFC was less active under constraint than unconstraint conditions. Moreover, both task-related and resting-state functional connectivity analyses indicated weaker coupling between PFC and temporal region in the SAT than in the HC group. Furthermore, left DLPFC mediated the effect of smartphone addiction on creative performance. These findings provide unprecedented neuroimaging evidence on the negative impact of smartphone addiction on creative cognition.

Brain correlates of subjective cognitive complaints in COVID-19 survivors: A multimodal magnetic resonance imaging study.

Cognitive impairment represents a leading residual symptom of COVID-19 infection, which lasts for months after the virus clearance. Up-to-date scientific reports documented a wide spectrum of brain changes in COVID-19 survivors following the illness's resolution, mainly related to neurological and neuropsychiatric consequences. Preliminary insights suggest abnormal brain metabolism, microstructure, and functionality as neural under-layer of post-acute cognitive dysfunction. While previous works focused on brain correlates of impaired cognition as objectively assessed, herein we investigated long-term neural correlates of subjective cognitive decline in a sample of 58 COVID-19 survivors with a multimodal imaging approach. Diffusion Tensor Imaging (DTI) analyses revealed widespread white matter disruption in the sub-group of cognitive complainers compared to the non-complainer one, as indexed by increased axial, radial, and mean diffusivity in several commissural, projection and associative fibres. Likewise, the Multivoxel Pattern Connectivity analysis (MVPA) revealed highly discriminant patterns of functional connectivity in resting-state among the two groups in the right frontal pole and in the middle temporal gyrus, suggestive of inefficient dynamic modulation of frontal brain activity and possible metacognitive dysfunction at rest. Beyond COVID-19 actual pathophysiological brain processes, our findings point toward brain connectome disruption conceivably translating into clinical post-COVID cognitive symptomatology. Our results could pave the way for a potential brain signature of cognitive complaints experienced by COVID-19 survivors, possibly leading to identify early therapeutic targets and thus mitigating its detrimental long-term impact on quality of life in the post-COVID-19 stages.

Brain functional connectivity alterations associated with neuropsychological performance 6-9 months following SARS-CoV-2 infection.

Neuropsychological deficits and brain damage following SARS-CoV-2 infection are not well understood. Then, 116 patients, with either severe, moderate, or mild disease in the acute phase underwent neuropsychological and olfactory tests, as well as completed psychiatric and respiratory questionnaires at 223 ± 42 days postinfection. Additionally, a subgroup of 50 patients underwent functional magnetic resonance imaging. Patients in the severe group displayed poorer verbal episodic memory performances, and moderate patients had reduced mental flexibility. Neuroimaging revealed patterns of hypofunctional and hyperfunctional connectivities in severe patients, while only hyperconnectivity patterns were observed for moderate. The default mode, somatosensory, dorsal attention, subcortical, and cerebellar networks were implicated. Partial least squares correlations analysis confirmed specific association between memory, executive functions performances and brain functional connectivity. The severity of the infection in the acute phase is a predictor of neuropsychological performance 6-9 months following SARS-CoV-2 infection. SARS-CoV-2 infection causes long-term memory and executive dysfunctions, related to large-scale functional brain connectivity alterations.

Risk of insomnia during COVID-19: effects of depression and brain functional connectivity.

Normal sleepers may be at risk for insomnia during COVID-19. Identifying psychological factors and neural markers that predict their insomnia risk, as well as investigating possible courses of insomnia development, could lead to more precise targeted interventions for insomnia during similar public health emergencies. Insomnia severity index of 306 participants before and during COVID-19 were employed to determine the development of insomnia, while pre-COVID-19 psychometric and resting-state fMRI data were used to explore corresponding psychological and neural markers of insomnia development. Normal sleepers as a group reported a significant increase in insomnia symptoms after COVID-19 outbreak (F = 4.618, P = 0.0102, df = 2, 609.9). Depression was found to significantly contribute to worse insomnia (ß = 0.066, P = 0.024). Subsequent analysis found that functional connectivity between the precentral gyrus and middle/inferior temporal gyrus mediated the association between pre-COVID-19 depression and insomnia symptoms during COVID-19. Cluster analysis identified that postoutbreak insomnia symptoms followed 3 courses (lessened, slightly worsened, and developed into mild insomnia), and pre-COVID-19 depression symptoms and functional connectivities predicted these courses. Timely identification and treatment of at-risk individuals may help avoid the development of insomnia in the face of future health-care emergencies, such as those arising from COVID-19 variants.

True grit and brain: Trait grit mediates the connection of DLPFC functional connectivity density to posttraumatic growth following COVID-19.

BACKGROUND: There is increasing interest in identifying factors to predict posttraumatic growth (PTG), a positive psychological response following traumatic events (e.g., the COVID-19 pandemic). Grit, a psychological trait of perseverance and passion to pursue long-term goals, has emerged as a promising predictor for PTG. This study aimed to examine the functional connectivity markers of grit and the potential brain-grit mechanism in predicting PTG. METHODS: Baseline brain imaging scans and grit scale and other controlling measures were administered in 100 normal young adults before the COVID-19 pandemic, and follow-up PTG measurement was obtained during the period of community-level outbreak. Whole-brain correlation analysis and prediction analysis were used to identify the brain regions whose functional connectivity density (FCD) related to individuals' grit scores. Mediation analyses were performed to explore the mediation relation between FCD, grit and PTG. RESULTS: Grit was positively related to FCD in the right dorsolateral prefrontal cortex (DLPFC), a core hub implicated in self-regulation and reward-motivation processes. Furthermore, grit mediated the effect of right DLPFC FCD on COVID-related PTG. These results survived controlling for self-control and family socioeconomic status. LIMITATIONS: Our study is limited by only one-session neuroimaging data and self-reported behavioral measures in a sample of normal adults. CONCLUSIONS: This study indicates grit and right DLPFC FCD as neuropsychological contributors for the development of PTG. It deepens our understanding of the neural bases of grit, and may have clinical potential to develop targeted brain interventions aimed at improving grit to raise PTG and mental health during the pandemic.

Reliability and similarity of resting state functional connectivity networks imaged using wearable, high-density diffuse optical tomography in the home setting.

BACKGROUND: When characterizing the brain's resting state functional connectivity (RSFC) networks, demonstrating networks' similarity across sessions and reliability across different scan durations is essential for validating results and possibly minimizing the scanning time needed to obtain stable measures of RSFC. Recent advances in optical functional neuroimaging technologies have resulted in fully wearable devices that may serve as a complimentary tool to functional magnetic resonance imaging (fMRI) and allow for investigations of RSFC networks repeatedly and easily in non-traditional scanning environments. METHODS: Resting-state cortical hemodynamic activity was repeatedly measured in a single individual in the home environment during COVID-19 lockdown conditions using the first ever application of a 24-module (72 sources, 96 detectors) wearable high-density diffuse optical tomography (HD-DOT) system. Twelve-minute recordings of resting-state data were acquired over the pre-frontal and occipital regions in fourteen experimental sessions over three weeks. As an initial validation of the data, spatial independent component analysis was used to identify RSFC networks. Reliability and similarity scores were computed using metrics adapted from the fMRI literature. RESULTS: We observed RSFC networks over visual regions (visual peripheral, visual central networks) and higher-order association regions (control, salience and default mode network), consistent with previous fMRI literature. High similarity was observed across testing sessions and across chromophores (oxygenated and deoxygenated haemoglobin, HbO and HbR) for all functional networks, and for each network considered separately. Stable reliability values (described here as a <10% change between time windows) were obtained for HbO and HbR with differences in required scanning time observed on a network-by-network basis. DISCUSSION: Using RSFC data from a highly sampled individual, the present work demonstrates that wearable HD-DOT can be used to obtain RSFC measurements with high similarity across imaging sessions and reliability across recording durations in the home environment. Wearable HD-DOT may serve as a complimentary tool to fMRI for studying RSFC networks outside of the traditional scanning environment and in vulnerable populations for whom fMRI is not feasible.

Associations between early-life stress exposure and internalizing symptomatology during the COVID-19 pandemic: Assessing the role of neurobehavioral mediators.

Background: The ongoing COVID-19 pandemic is a major stressor that has been associated with increased risk for psychiatric illness in the general population. Recent work has highlighted that experiences of early-life stress (ELS) may impact individuals' psychological functioning and vulnerability for developing internalizing psychopathology in response to pandemic-related stress. However, little is known about the neurobehavioral factors that may mediate the association between ELS exposure and COVID-related internalizing symptomatology. The current study sought to examine the mediating roles of pre-pandemic resting-state frontoamygdala connectivity and concurrent emotion regulation (ER) in the association between ELS and pandemic-related internalizing symptomatology. Methods: Retrospective life-stress histories, concurrent self-reported ER strategies (i.e., reappraisal and suppression), concurrent self-reported internalizing symptomatology (i.e., depression- and anxiety-related symptomatology), and resting-state functional connectivity data from a sample of adults (N = 64, M age = 22.12, female = 68.75%) were utilized. Results: There were no significant direct associations between ELS and COVID-related internalizing symptomatology. Neither frontoamygdala functional connectivity nor ER strategy use mediated an association between ELS and COVID-related internalizing symptomatology (ps > 0.05). Exploratory analyses identified a significant moderating effect of reappraisal use on the association between ELS and internalizing symptomatology (ß = -0.818, p = 0.047), such that increased reappraisal use buffered the impact of ELS on psychopathology. Conclusions: While frontoamygdala connectivity and ER do not appear to mediate the association between ELS and COVID-related internalizing symptomatology, our findings suggest that the use of reappraisal may buffer against the effect of ELS on mental health during the pandemic.

Gender Differences in Hippocampal/Parahippocampal Functional Connectivity Network in Patients Diagnosed with Chronic Insomnia Disorder.

Background: Gender differences in hippocampal and parahippocampal gyrus (HIP/PHG) volumes have been reported in sleep disorders. Therefore, this study investigated the moderating effect of gender on the relationship between chronic insomnia disorder (CID) and the HIP/PHG functional connectivity (FC) network. Methods: For this study, 110 patients diagnosed with CID (43 men and 67 women) and 60 matched good sleep control (GSC) (22 men and 38 women) were recruited. These participants underwent resting-state functional magnetic resonance imaging scans, after which a 2 × 2 (diagnosis × gender) analysis of variance was used to detect the main and interactive effect of insomnia and gender on their HIP/PHG FC networks. Results: Although the main effect of insomnia on the HIP FC network was observed in the bilateral cerebellar tonsil, superior frontal gyrus, and the medial orbitofrontal cortex, effects on the PHG FC network were observed in the bilateral HIP and amygdala. In contrast, the main effect of gender on the HIP FC network was observed in the right cerebellum posterior lobe, the dorsolateral prefrontal cortex (DLPFC), and the supplemental motor area. Of note, the interactive effect of both insomnia and gender was observed in FCs between the right HIP and the dorsal anterior cingulate cortex, and then between the right PHG and DLPFC. Moreover, the FC between the right PHG and left DLPFC was positively associated with anxiety scores in the female patients with CID. Conclusion: Our study identified that gender differences in brain connectivity existed between the HIP/PHG and executive control network in patients diagnosed with CID, these results will eventually extend our understanding of the important role that gender plays in the pathophysiology of CID.

Prenatal Maternal Distress During the COVID-19 Pandemic and Associations With Infant Brain Connectivity.

BACKGROUND: The COVID-19 pandemic has caused substantially elevated distress in pregnant individuals, which has the potential to affect the developing infant brain. Our main objective was to understand how prenatal distress was related to infant brain structure and function and whether social support moderated the associations. METHODS: The Pregnancy during the COVID-19 Pandemic (PdP) cohort study collected Patient-Reported Outcomes Measurement Information System Anxiety scale, Edinburgh Postnatal Depression Scale, and Social Support Effectiveness Questionnaire data from a population-based sample of pregnant individuals living in Canada (N = 8602). For a subsample of participants, their infants (n = 75) underwent magnetic resonance imaging at 3 months of age to examine whether prenatal maternal distress was associated with infant brain architecture, including the role of social support as a potential protective factor. RESULTS: Overall, 33.4% of participants demonstrated clinically elevated depression symptoms and 47.1% of participants demonstrated clinically elevated anxiety symptoms. We identified lower social support as a significant predictor of clinically elevated prenatal maternal distress (t8598 = -22.3, p < .001). Fifty-eight diffusion image datasets (20 female/38 male, 92 ± 14 days old) and 41 functional datasets (13 female/28 male, 92 ± 14 days old) were included in our analysis after removal of poor-quality images and infants without postpartum maternal distress scores. We found significant relationships between prenatal maternal distress and infant amygdala-prefrontal microstructural and functional connectivity measures, and we demonstrate for the first time that social support moderates these relationships. CONCLUSIONS: Our findings suggest a potentially long-lasting impact of the COVID-19 pandemic on children and show that social support acts as a possible mediator not just for pregnant individuals but also developing infants. These findings provide timely evidence to inform clinical practice and policy surrounding the care of pregnant individuals and highlight the importance of social support.

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.