Global Functional Connectivity Research Articles

Crochet increases attention through a requiring motor skill learning

In this study, we compared the effects promoted by a brief single session of crochet in a group of skilled knitters (CRO) and a control group (CRT) on the Attentional Network Test (ANT) and the whole brain Functional Connectivity (FC) revealed by Magnetoencephalography (MEG). Data revealed that crochet determined a significant effect (before, T0, vs after, T1, the crochet session) on reaction times (for all cue and stimulus types), improving alertness and orienting networks (but not executive control) only in the CRO group. Data of FC are coherent with the behavioural ones. We observed that the Betweenness Centrality maximum (BCmax) index in the beta band significantly increased, and global FC in the alpha band significantly increased at T1 for the CRO group but not for the CTR group. Increased global BCmax in the beta band after the crochet activity correlated with better performance (reduced reaction times), suggesting that the brain has become more efficiently integrated, thus increasing the information exchange between different brain areas. Decreased global FC in the alpha band may reflect a transition from a quiet, global rest to a condition of increased alertness and readiness to stimuli. Finally, we discuss the hypothesis that these results could be the reinforcement of connections between motor and attentional networks promoted by learning the complex motor skills of crochet.

Basal forebrain global functional connectivity is preserved in asymptomatic presenilin-1 E280A mutation carriers: Results from the Colombia cohort.

Imaging studies showed early atrophy of the cholinergic basal forebrain in prodromal sporadic Alzheimer's disease and reduced posterior basal forebrain functional connectivity in amyloid positive individuals with subjective cognitive decline. Similar investigations in familial cases of Alzheimer's disease are still lacking. To test whether presenilin-1 E280A mutation carriers have reduced basal forebrain functional connectivity and whether this is linked to amyloid pathology. This is a cross-sectional study that analyzes baseline functional imaging data. We obtained data from the Colombia cohort Alzheimer's Prevention Initiative Autosomal-Dominant Alzheimer's Disease Trial. We analyzed data from 215 asymptomatic subjects carrying the presenilin-1 E280A mutation [64% female; 147 carriers (M = 35 years), 68 noncarriers (M = 40 years)]. We extracted functional magnetic resonance imaging data using seed-based connectivity analysis to examine the anterior and posterior subdivisions of the basal forebrain. Subsequently, we performed a Bayesian Analysis of Covariance to assess the impact of carrier status on functional connectivity in relation to amyloid positivity. For comparison, we also investigated hippocampus connectivity. We found no effect of carrier status on anterior (Bayesian Factor10 = 1.167) and posterior basal forebrain connectivity (Bayesian Factor10 = 0.033). In carriers, we found no association of amyloid positivity with basal forebrain connectivity. We falsified the hypothesis of basal forebrain connectivity reduction in preclinical mutation carriers with amyloid pathology. If replicated, these findings may not only confirm a discrepancy between familial and sporadic Alzheimer's disease, but also suggest new potential targets for future treatments.

Altered brain functional connectivity in patients with tension-type headache.

To evaluate whether patients with tension-type headache (TTH) exhibit abnormal brain functional connectivity compared to healthy controls. TTH is one of the most prevalent headache disorders throughout the world. The present study delves into brain functional connectivity in patients with TTH to enhance the understanding of its underlying pathophysiology. A cross-sectional study was conducted, enrolling patients with TTH diagnosed in line with the International Classification of Headache Disorders, 3rd edition beta criteria and a cohort of healthy controls (HCs). We used four metrics-global brain functional connectivity, functional connectivity, Granger causality analysis, and dynamic functional connectivity-to evaluate alterations of functional connectivity patterns in patients with TTH from both static and dynamic perspectives. Furthermore, correlational analyses were performed to explore the relationships between abnormal brain activities and clinical characteristics. A total of 33 patients with TTH (mean age = 42.3; 13 males/20 females) and 30 HCs (mean age = 37.1; 13 males/17 females) were included in the current study. Compared to HCs, patients with TTH showed altered global brain functional connectivity in the right dorsolateral superior frontal gyrus (SFGdor, t = 4.60). Abnormal functional connectivity was also detected between the right SFGdor and the right superior temporal gyrus (t = 4.56). Furthermore, the right SFGdor exhibited altered information flow with several brain regions, including the left precuneus (t = 5.16), right middle temporal gyrus (MTG, t = 4.72/-4.41), right inferior temporal gyrus (t = 4.64), right caudate nucleus (t = 4.09), and right thalamus (THA, t = -4.04). In terms of dynamic functional connectivity, disconnection was observed between the right SFGdor and the right MTG (t = -3.10), right Rolandic operculum (ROL, t = 3.60), left opercular inferior frontal gyrus (t = -3.48), and left medial superior frontal gyrus (t = -3.00). In addition, the correlation analyses revealed that activities in the MTG (r = 0.48), THA (r = -0.38), and ROL (r = 0.36) were significantly correlated with disease duration, while THA activity was associated with Visual Analogue Scale scores (r = 0.50). This study revealed alterations in both static and dynamic brain functional connectivity in patients with TTH within regions implicated in sensory perception, emotional processing, cognition, and pain regulation. These results may promote the understanding of the neural networks involved in TTH and potentially inform future therapeutic approaches for the condition.

Alterations in local activity and whole-brain functional connectivity in human immunodeficiency virus-associated neurocognitive disorders: a resting-state functional magnetic resonance imaging study.

Approximately half of human immunodeficiency virus (HIV) patients experience HIV-associated neurocognitive disorders (HAND); however, the neurophysiological mechanisms underlying HAND remain unclear. This study aimed to evaluate changes in functional brain activity patterns during the early stages of HIV infection by comparing local and global indicators using resting-state functional magnetic resonance imaging (rs-fMRI). A total of 165 people living with HIV (PLWH) but without neurocognitive disorders (PWND), 173 patients with asymptomatic neurocognitive impairment (ANI), and 100 matched healthy controls (HCs) were included in the study. A cross-sectional study of the participants was conducted. The metrics of functional segregation and integration were computed, using graph theory to explore differences across methodologies. Brain functional changes in the PWND and ANI groups were assessed, and correlations between the rs-fMRI metrics, clinical data, and cognitive function were examined. As cognitive function declined, changes reflected by regional homogeneity (ReHo) were primarily observed in the default mode network (DMN). In the DMN and visual network (VIS), amplitude of low-frequency fluctuation (ALFF) decreases were mainly observed in the parieto-occipital lobes, while increases were mainly observed in the limbic network (LIM). Reductions in fractional ALFF (fALFF) were mainly observed in the somatomotor network (SMN) and LIM, while increases were observed in the DMN and LIM. Unlike local indicators, global functional connectivity (FC) significantly decreased in both the PWND and ANI groups compared to the HC group. The ANI group showed partial increases in FC compared to the PWND group, with major changes observed in the DMN, VIS, and LIM. Notably, FC between the right insula and right supramarginal gyrus decreased significantly following HIV infection, while FC between the right caudate nucleus and the left middle frontal gyrus declined further in the ANI group. Graph theory further confirmed the significance of the DMN, and revealed changes in the eigenvector centrality mapping (ECM) values of the frontoparietal network (FPN) and dorsal attention network (DAN). HIV patients exhibit complex changes in both local and global brain activity, regardless of cognitive impairment. Widespread abnormalities primarily involve the DMN, VIS, and LIM. Changes in FC along the fronto-striatal pathway may play a crucial role in the decline of cognitive function in individuals with HAND. Our findings provide new insights that may assist in the early detection of brain damage in the early stages of HIV infection. The use of multiple methodologies may offer a more comprehensive and effective approach, enabling the early detection of brain damage in HIV patients.

Multimodal neurophenomenology of advanced concentration absorption meditation: An intensively sampled case study of Jhana.

Using a combination of fMRI, EEG, and phenomenology ratings, we examined the neurophenomenology of advanced concentrative absorption meditation, namely jhanas (ACAM-J), in a practitioner with over 23,000 h of meditation practice. Our study shows that ACAM-J states induce reliable changes in conscious experience and that these experiences are related to neural activity. Using resting-state fMRI functional connectivity, we found that ACAM-J is associated with decreased within-network modularity, increased global functional connectivity (GFC), and desegregation of the default mode and visual networks. Compared to control tasks, the ACAM-J were also related to widespread decreases in broadband EEG oscillatory power and increases in Lempel-Ziv complexity (LZ, a measure of brain entropy). Some fMRI findings varied by the control task used, while EEG results remained consistent, emphasizing both shared and unique neural features of ACAM-J. These differences in fMRI and EEG-measured neurophysiological properties correlated with specific changes in phenomenology - and especially with ACAM-J-induced states of bliss - enriching our understanding of these advanced meditative states. Our results show that advanced meditation practices markedly dysregulate high-level brain systems via practices of enhanced attention to sensations, corroborating recent neurocognitive theories of meditation as the deconstruction of the brain's cortical hierarchy. Overall, our results suggest that ACAM-J is associated with the modulation of large-scale brain networks in both fMRI and EEG, with potential implications for understanding the mechanisms of deep concentration practices and their effects on subjective experience.

Multi-view brain functional connectivity and hierarchical fusion for EEG-based emotion recognition

Emotional states evolve gradually from their onset to full manifestation, reflected in changes in brain functional connectivity. Existing research often focuses only on the final emotional state, missing the rich, dynamic information of emotional evolution. This paper proposes a novel network framework leveraging global and local brain functional connectivity through a multi-view approach. We introduce a global and local connectivity modeling method using electroencephalogram signals to simulate brain connectivity changes across time and specific moments. A residual-based local detail feature extractor combined with a coordinate attention module captures long-range dependencies and maintains positional accuracy. A global feature extractor is also designed for the effective extraction of emotional information. Finally, a hierarchical multi-scale cross-attention feature fusion module integrates features across different levels to enhance emotion recognition performance and robustness. Extensive experiments on three publicly available datasets demonstrate the framework’s superiority and generalization capability.

Relationship Between Structural and Functional Network Connectivity Changes for Patients With Traumatic Brain Injury and Chronic Health Symptoms.

Combination of structural and functional brain connectivity methods provides a more complete and effective avenue into the investigation of cortical network responses to traumatic brain injury (TBI) and subtle alterations in brain connectivity associated with TBI. Structural connectivity (SC) can be measured using diffusion tensor imaging to evaluate white matter integrity, whereas functional connectivity (FC) can be studied by examining functional correlations within or between functional networks. In this study, the alterations of SC and FC were assessed for TBI patients, with and without chronic symptoms (TBIcs/TBIncs), compared with a healthy control group (CG). The correlation between global SC and FC was significantly increased for both TBI groups compared with CG. SC was significantly lower in the TBIcs group compared with CG, and FC changes were seen in the TBIncs group compared with CG. When comparing TBI groups, FC differences were observed in the TBIcs group compared with the TBIncs group. These observations show that the presence of chronic symptoms is associated with a distinct pattern of SC and FC changes including the atrophy of the SC and a mixture of functional hypoconnectivity and hyperconnectivity, as well as loss of segregation of functional networks.

Global functional connectivity reorganization reflects cognitive processing speed deficits and fatigue in multiple sclerosis.

Cognitive impairment (CI) in multiple sclerosis (MS) is associated with bidirectional changes in resting-state centrality measures. However, practicable functional magnetic resonance imaging (fMRI) biomarkers of CI are still lacking. The aim of this study was to assess the graph-theory-based degree rank order disruption index (kD) and its association with cognitive processing speed as a marker of CI in patients with MS (PwMS) in a secondary cross-sectional fMRI analysis. Differentiation between PwMS and healthy controls (HCs) using kD and its correlation with CI (Symbol Digit Modalities Test) was compared to established imaging biomarkers (regional degree, volumetry, diffusion-weighted imaging, lesion mapping). Additional associations were assessed for fatigue (Fatigue Scale for Motor and Cognitive Functions), gait and global disability. Analysis in 56 PwMS and 58 HCs (35/27 women, median age 45.1/40.5 years) showed lower kD in PwMS than in HCs (median -0.30/-0.06, interquartile range 0.55/0.54; p = 0.009, Mann-Whitney U test), yielding acceptable yet non-superior differentiation (area under curve 0.64). kD and degree in medial prefrontal cortex (MPFC) correlated with CI (kD/MPFC Spearman's ρ = 0.32/-0.45, p = 0.019/0.001, n = 55). kD also explained fatigue (ρ = -0.34, p = 0.010, n = 56) but neither gait nor disability. kD is a potential biomarker of CI and fatigue warranting further validation.

Complex memories induced by intracranial electrical brain stimulation are related to complex networks.

The precise and fleeting moment of rich recollection triggered by an environmental cue is difficult to reproduce in the lab. However, epilepsy patients can experience sudden reminiscences after intracranial electrical brain stimulation (EBS). In these cases, the transient brain state related to the activation of the engram and its conscious perception can be recorded using intracerebral EEG (iEEG). We collected various EBS-induced reminiscences for iEEG analysis, classifying them as follows: no or weak details (familiarity); moderate details and context (semantic and personal semantic memories); high details and context (episodic). Nine brain areas were selected within the temporal lobes (including the hippocampus and temporal neocortex, ipsi- and contralateral) and the insula, defining a network (each area as a node). Functional connectivity was measured by estimating pair-wise non-linear correlations between signals recorded from these brain regions during different memory events. Seventeen reminiscences in six patients (2 episodic, 10 personal semantic, 2 semantic memories, 5 familiar objects, 1 déjà-rêvé) were compared to 18 control experiential phenomena (unrelated to reminiscence), 18 negative EBS (which failed to elicit memories or other phenomena) in the same locations, and pre-EBS baseline activity. The global functional connectivity in the network was higher following EBS-induced reminiscences than during baseline activity, control phenomena, or negative EBS. The degree of connectivity increased with the complexity of memories; it was higher for detailed and contextualized memories like episodic memories. More significant links compared to baseline (edges with higher non-linear correlation relative to baseline) were observed for episodic memories than for less contextualized memories. These increases in connectivity occurred in all frequency bands, except the delta band. Our results support understanding declarative memory retrieval as having a multiplexed organization. They also show that richer memories activated by intracranial EBS are related to more complex connectivity patterns across medial and neocortical temporal lobe structures.

Unravelling excitation/inhibition imbalance in early and familial Alzheimer's Disease

AbstractBackgroundAn early disruption in excitation‐inhibition (E‐I) balance is believed to underlie abnormal local and global network dynamics in Alzheimer’s disease (AD). While prior studies proposed that changes in E‐I balance may underlie the established slowing of oscillatory activity and changes in functional connectivity in symptomatic AD, the specific alterations occurring in the presymptomatic stage of AD remain poorly understood. This study aims to identify local and global spectral power and functional connectivity changes in individuals with familial AD before the onset of clinical symptoms.MethodResting‐state magnetoencephalography (MEG) recordings were conducted in a unique cohort of cognitively unimpaired individuals carrying autosomal dominant mutations in the APP and PSEN1 genes (n = 11), leading to early‐onset AD. Each mutation carrier was demographically matched with three cognitively healthy subjects (HCs) without mutations and with available MEG. We compared source‐level whole‐brain average and regional spectral power and volume‐conduction corrected functional connectivity measures across different frequency bands. Hub vulnerability was assessed using the hub disruption index. Significant MEG measures were correlated with age, estimated years before symptom onset (EYBSO), and cognitive performance.ResultCognitively normal mutation carriers exhibited signatures of oscillatory slowing, characterized by a widespread higher relative power in the theta band (4‐8 Hz) and a lower parieto‐temporal‐occipital peak frequency compared to HCs. Additionally, they presented frequency‐ and degree‐dependent functional connectivity changes: higher phase‐based functional connectivity in the theta band in initial low‐degree regions (as determined by weighted degree in HCs), but lower global amplitude‐based functional connectivity in the alpha (8‐13 Hz) and beta (13‐30 Hz) bands compared to HCs, most strongly in initial high‐degree regions. No correlations between MEG measures and age, EYBSO, or cognitive indices were found after correction for multiple comparisons.ConclusionNeurophysiological changes occur before the onset of cognitive symptoms in individuals carrying mutations in the APP or PSEN1 genes. These changes include oscillatory slowing and frequency‐ and degree‐dependent functional connectivity alterations, mirroring alterations observed in clinical stages of AD and suggesting an early E‐I imbalance. These findings contribute to a comprehensive understanding of presymptomatic pathophysiological alterations in AD.

α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor density underlies intraregional and interregional functional centrality.

Local and global functional connectivity densities (lFCD and gFCD, respectively), derived from functional magnetic resonance imaging (fMRI) data, represent the degree of functional centrality within local and global brain networks. While these methods are well-established for mapping brain connectivity, the molecular and synaptic foundations of these connectivity patterns remain unclear. Glutamate, the principal excitatory neurotransmitter in the brain, plays a key role in these processes. Among its receptors, the α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor (AMPAR) is crucial for neurotransmission, particularly in cognitive functions such as learning and memory. This study aimed to examine the association of the AMPAR density and FCD metrics of intraregional and interregional functional centrality. Using [11C]K-2, a positron emission tomography (PET) tracer specific for AMPARs, we measured AMPAR density in the brains of 35 healthy participants. Our findings revealed a strong positive correlation between AMPAR density and both lFCD and gFCD-lFCD across the entire brain. This correlation was especially notable in key regions such as the anterior cingulate cortex, posterior cingulate cortex, pre-subgenual frontal cortex, Default Mode Network, and Visual Network. These results highlight that postsynaptic AMPARs significantly contribute to both local and global functional connectivity in the brain, particularly in network hub regions. This study provides valuable insights into the molecular and synaptic underpinnings of brain functional connectomes.

Global changes in the pattern of connectivity in developmental prosopagnosia.

Developmental prosopagnosia is a neurodevelopmental condition characterized by difficulties in recognizing the identity of a person from their face. While current theories of the neural basis of developmental prosopagnosia focus on the face processing network, successful recognition of face identities requires broader integration of neural signals across the whole brain. Here, we asked whether disruptions in global functional and structural connectivity contribute to the face recognition difficulties observed in developmental prosopagnosia. We found that the left temporal pole was less functionally connected to the rest of the brain in developmental prosopagnosia. This was driven by weaker contralateral connections to the middle and inferior temporal gyri, as well as to the medial prefrontal cortex. The pattern of global connectivity in the left temporal pole was also disrupted in developmental prosopagnosia. Critically, these changes in global functional connectivity were only evident when participants viewed faces. Structural connectivity analysis revealed localized reductions in connectivity between the left temporal pole and a number of regions, including the fusiform gyrus, inferior temporal gyrus, and orbitofrontal cortex. Our findings underscore the importance of whole-brain integration in supporting typical face recognition and provide evidence that disruptions in connectivity involving the left temporal pole may underlie the characteristic difficulties of developmental prosopagnosia.

Neural Correlates of Psychedelic, Sleep, and Sedated States Support Global Theories of Consciousness.

Understanding neural mechanisms of consciousness remains a challenging question in neuroscience. A central debate in the field concerns whether consciousness arises from global interactions that involve multiple brain regions or focal neural activity, such as in sensory cortex. Additionally, global theories diverge between the Global Neuronal Workspace (GNW) hypothesis, which emphasizes frontal and parietal areas, and the Integrated Information Theory (IIT), which focuses on information integration within posterior cortical regions. To disentangle the global vs. local and frontoparietal vs. posterior dilemmas, we measured global functional connectivity and local neural synchrony with functional magnetic resonance imaging (fMRI) data across a spectrum of conscious states in humans induced by psychedelics, sleep, and deep sedation. We found that psychedelic states are associated with increased global functional connectivity and decreased local neural synchrony. In contrast, non-REM sleep and deep sedation displayed the opposite pattern, suggesting that consciousness arises from global brain network interactions rather than localized activity. This mirror-image pattern between enhanced and diminished states was observed in both anterior-posterior (A-P) and posterior-posterior (P-P) brain regions but not within the anterior part of the brain alone. Moreover, anterior transmodal regions played a key role in A-P connectivity, while both posterior transmodal and posterior unimodal regions were critical for P-P connectivity. Overall, these findings provide empirical evidence supporting global theories of consciousness in relation to varying states of consciousness. They also bridge the gap between two prominent theories, GNW and IIT, by demonstrating how different theories can converge on shared neuronal mechanisms.

Correlations between alterations in global brain functional connectivity in patients with major depressive disorder and their genetic characteristics

This study aims to elucidate the neuroimaging changes associated with major depressive disorder (MDD) and their relationship with genetic characteristics. We conducted a global-brain functional connectivity (GFC) and genetic-neuroimaging correlation analysis on 42 MDD patients and 42 healthy controls (HCs), exploring the correlation between GFC abnormalities and clinical variables. Results showed that compared to HCs, MDD patients had significantly decreased GFC values in the bilateral posterior cingulate cortex/precuneus and increased GFC values in the left and right cerebellum Crus I/II. Additionally, a negative correlation was observed between the GFC values of the left cerebellum Crus I/II and subjective support scores, as well as social support revalued scale total scores. We identified genes associated with GFC changes in MDD, which are enriched in biological processes such as synaptic transmission and ion transport. Our findings indicate the presence of abnormal GFC values in severe depression, complementing the pathological research on the condition. Furthermore, this study provides preliminary evidence for the correlation between social support levels and brain functional connectivity, offering insights into the potential association between GFC changes and gene expression in MDD patients.

Alternations voxel-wise interhemispheric and intrahemipheric functional connectivity dynamics in internet gaming disorder

BackgroundCurrently, numerous studies have indicated that individuals with internet gaming disorder (IGDs) have aberrant functional connection patterns between multiple brain regions and networks. However, temporal variability in the intra- and interhemispheric dynamic functional connectivity in IGDs remains unknown. MethodsThis study investigated resting-state functional magnetic resonance data from 55 IGDs and 50 demographically matched healthy controls (HCs). Functional connectivity density (FCD) combined with sliding window analysis is employed to calculate the temporal variability of global functional connectivity. The temporal variability of dynamic functional connectivity further quantified utilizing the standard deviations of global, intra-, and interhemispheric FCD. Finally, correlation analyses were performed between dynamic FCD varience (dFCD) in differential brain regions and clinical behaviors. ResultIGDs showed decreased intra- and interhemispheric dFCD variance in the visual attention network (precuneus and calcarine) and also demonstrated hemispheric-level dFCD variance abnormalities in the posterior cingulate cortex (PCC) compared to HCs. Moreover, abnormal global dFCD variability of the calcarine and ipsilateral dFCD variability of the PCC were negatively correlated with the severity of IGDs in the IGD group. ConclusionOur results demonstrate abberant intra- and interhemispheric dynamic functional connectivity in the visual attention network, which emphasizes the neurobiological basis for impaired concentration in IGDs.

The distinct functional brain network and its association with psychotic symptom severity in men with methamphetamine-associated psychosis

BackgroundIndividuals using methamphetamine (METH) may experience psychosis, which usually requires aggressive treatment. Studies of the neural correlates of METH-associated psychosis (MAP) have focused predominantly on the default mode network (DMN) and cognitive control networks. We hypothesize that METH use alters global functional connections in resting-state brain networks and that certain cross-network connections could be associated with psychosis.MethodsWe recruited 24 healthy controls (CRL) and 54 men with METH use disorder (MUD) who were then divided into 25 without psychosis (MNP) and 29 with MAP. Psychotic symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS), evaluating (1) large-scale alterations in regional-wise resting-state functional connectivity (rsFC) across 11 brain networks and (2) associations between rsFC and psychotic symptom severity.ResultsThe MUD group exhibited greater rsFC between the salience network (SN)-DMN, and subcortical network (SCN)-DMN compared to the CRL group. The MAP group exhibited decreased rsFC in the sensory/somatomotor network (SMN)-dorsal attention network (DAN), SMN-ventral attention network (VAN), SMN-SN, and SMN-auditory network (AN), whereas the MNP group exhibited increased rsFC in the SMN-DMN and the frontoparietal network (FPN)-DMN compared to CRL. Additionally, the MAP group exhibited decreased rsFC strength between the SMN-DMN, SMN-AN, SMN-FPN, and DMN-VAN compared to the MNP group. Furthermore, across the entire MUD group, the PANSS-Positive subscale was negatively correlated with the DMN-FPN and FPN-SMN, while the PANSS-Negative subscale was negatively correlated with the DMN-AN and SMN-SMN.ConclusionMUD is associated with altered global functional connectivity. In addition, the MAP group exhibits a different brain functional network compared to the MNP group.

Interactive effect of air pollution and genetic risk of depression on processing speed by resting-state functional connectivity of occipitoparietal network

BackgroundAir pollution, a reversible environmental factor, was significantly associated with the cognitive domains that are impaired in major depressive disorder (MDD), notably processing speed. Limited evidence explores the interactive effect of air pollution and the genetic risk of depression on cognition. This cross-sectional study aims to extend the research by specifically examining how this interaction influences depression-related cognitive impairment and resting-state brain function.MethodsEligible participants were 497 healthy adult volunteers (48.7% males, mean age 24.5) living in Beijing for at least 1 year and exposed to relatively high air pollution from the local community controlling for socioeconomic and genomic. Six months’ ambient air pollution exposures were assessed based on residential addresses using monthly averages of fine particulate matter with a diameter of less than or equal to 2.5 μm (PM2.5). A cross-sectional analysis was conducted using functional magnetic resonance imaging (fMRI) and cognitive performance assessments. The polygenic risk score (PRS) of MDD was used to estimate genetic susceptibility.ResultsUsing a general linear model and partial least square regression, we observed a negative association between resting-state local connectivity in precuneus and PRS-by-PM2.5 interactive effect (PFWE = 0.028), indicating that PM2.5 exposure reduced the spontaneous activity in precuneus in individuals at high genetic risk for MDD. DNA methylation and gene expression of the SLC30A3 gene, responsible for maintaining zinc-glutamate homeostasis, was suggestively associated with this local connectivity. For the global functional connectivity, the polygenic risk for MDD augmented the neural impact of PM2.5 exposure, especially in the frontal-parietal and frontal-limbic regions of the default mode network (PFDR < 0.05). In those genetically predisposed to MDD, increased PM2.5 exposure positively correlated with resting-state functional connectivity between the left angular gyrus and left cuneus gyrus. This connectivity was negatively associated with processing speed.ConclusionsOur cross-sectional study suggests that air pollution may be associated with an increased likelihood of cognitive impairment in individuals genetically predisposed to depression, potentially through alterations in the resting-state function of the occipitoparietal and default mode network.

Developmental changes in brain structure and function following exposure to oral LSD during adolescence

LSD is a hallucinogen with complex neurobiological and behavioral effects. Underlying these effects are changes in brain neuroplasticity. This is the first study to follow the developmental changes in brain structure and function following LSD exposure in periadolescence. We hypothesized LSD given during a time of heightened neuroplasticity, particularly in the forebrain, would affect cognitive and emotional behavior and the associated underlying neuroanatomy and neurocircuitry. Female and male mice were given vehicle, single or multiple treatments of 3.3 µg of LSD by oral gavage starting on postnatal day 51. Between postnatal days 90–120 mice were imaged and tested for cognitive and motor behavior. MRI data from voxel-based morphometry, diffusion weighted imaging, and BOLD resting state functional connectivity were registered to a mouse 3D MRI atlas with 139 brain regions providing site-specific differences in global brain structure and functional connectivity between experimental groups. Motor behavior and cognitive performance were unaffected by periadolescent exposure to LSD. Differences across experimental groups in brain volume for any of the 139 brain areas were few in number and not focused on any specific brain region. Multiple exposures to LSD significantly altered gray matter microarchitecture across much of the brain. These changes were primary associated with the thalamus, sensory and motor cortices, and basal ganglia. The forebrain olfactory system and prefrontal cortex and hindbrain cerebellum and brainstem were unaffected. The functional connectivity between forebrain white matter tracts and sensorimotor cortices and hippocampus was reduced with multidose LSD exposure. Does exposure to LSD in late adolescence have lasting effects on brain development? The bulk of our significant findings were seen through changes is DWI values across 74 brain areas in the multi-dose LSD group. The pronounced changes in indices of anisotropy across much of the brain would suggest altered gray matter microarchitecture and neuroplasticity. There was no evidence of LSD having consequential effects on cognitive or motor behavior when animal were evaluated as young adults 90–120 days of age. Neither were there any differences in the volume of specific brain areas between experimental conditions. The reduction in connectivity in forebrain white matter tracts with multidose LSD and consolidation around sensorimotor and hippocampal brain areas requires a battery of tests to understand the consequences of these changes on behavior.

Transcriptomic decoding of regional cortical vulnerability to major depressive disorder

Previous studies in small samples have identified inconsistent cortical abnormalities in major depressive disorder (MDD). Despite genetic influences on MDD and the brain, it is unclear how genetic risk for MDD is translated into spatially patterned cortical vulnerability. Here, we initially examined voxel-wise differences in cortical function and structure using the largest multi-modal MRI data from 1660 MDD patients and 1341 controls. Combined with the Allen Human Brain Atlas, we then adopted transcription-neuroimaging spatial correlation and the newly developed ensemble-based gene category enrichment analysis to identify gene categories with expression related to cortical changes in MDD. Results showed that patients had relatively circumscribed impairments in local functional properties and broadly distributed disruptions in global functional connectivity, consistently characterized by hyper-function in associative areas and hypo-function in primary regions. Moreover, the local functional alterations were correlated with genes enriched for biological functions related to MDD in general (e.g., endoplasmic reticulum stress, mitogen-activated protein kinase, histone acetylation, and DNA methylation); and the global functional connectivity changes were associated with not only MDD-general, but also brain-relevant genes (e.g., neuron, synapse, axon, glial cell, and neurotransmitters). Our findings may provide important insights into the transcriptomic signatures of regional cortical vulnerability to MDD.

Reliability of variability and complexity measures for task and task-free BOLD fMRI.

Brain activity continuously fluctuates over time, even if the brain is in controlled (e.g., experimentally induced) states. Recent years have seen an increasing interest in understanding the complexity of these temporal variations, for example with respect to developmental changes in brain function or between-person differences in healthy and clinical populations. However, the psychometric reliability of brain signal variability and complexity measures-which is an important precondition for robust individual differences as well as longitudinal research-is not yet sufficiently studied. We examined reliability (split-half correlations) and test-retest correlations for task-free (resting-state) BOLD fMRI as well as split-half correlations for seven functional task data sets from the Human Connectome Project to evaluate their reliability. We observed good to excellent split-half reliability for temporal variability measures derived from rest and task fMRI activation time series (standard deviation, mean absolute successive difference, mean squared successive difference), and moderate test-retest correlations for the same variability measures under rest conditions. Brain signal complexity estimates (several entropy and dimensionality measures) showed moderate to good reliabilities under both, rest and task activation conditions. We calculated the same measures also for time-resolved (dynamic) functional connectivity time series and observed moderate to good reliabilities for variability measures, but poor reliabilities for complexity measures derived from functional connectivity time series. Global (i.e., mean across cortical regions) measures tended to show higher reliability than region-specific variability or complexity estimates. Larger subcortical regions showed similar reliability as cortical regions, but small regions showed lower reliability, especially for complexity measures. Lastly, we also show that reliability scores are only minorly dependent on differences in scan length and replicate our results across different parcellation and denoising strategies. These results suggest that the variability and complexity of BOLD activation time series are robust measures well-suited for individual differences research. Temporal variability of global functional connectivity over time provides an important novel approach to robustly quantifying the dynamics of brain function. PRACTITIONER POINTS: Variability and complexity measures of BOLD activation show good split-half reliability and moderate test-retest reliability. Measures of variability of global functional connectivity over time can robustly quantify neural dynamics. Length of fMRI data has only a minor effect on reliability.