Dynamic Changes In Functional Connectivity Research Articles

Dynamic properties in functional connectivity changes and striatal dopamine deficiency in Parkinson's disease.

Recent studies in Parkinson's disease (PD) patients reported disruptions in dynamic functional connectivity (dFC, i.e., a characterization of spontaneous fluctuations in functional connectivity over time). Here, we assessed whether the integrity of striatal dopamine terminals directly modulates dFC metrics in two separate PD cohorts, indexing dopamine-related changes in large-scale brain network dynamics and its implications in clinical features. We pooled data from two disease-control cohorts reflecting early PD. From the Parkinson's Progression Marker Initiative (PPMI) cohort, resting-state functional magnetic resonance imaging (rsfMRI) and dopamine transporter (DaT) single-photon emission computed tomography (SPECT) were available for 63 PD patients and 16 age- and sex-matched healthy controls. From the clinical research group 219 (KFO) cohort, rsfMRI imaging was available for 52 PD patients and 17 age- and sex-matched healthy controls. A subset of 41 PD patients and 13 healthy control subjects additionally underwent 18F-DOPA-positron emission tomography (PET) imaging. The striatal synthesis capacity of 18F-DOPA PET and dopamine terminal quantity of DaT SPECT images were extracted for the putamen and the caudate. After rsfMRI pre-processing, an independent component analysis was performed on both cohorts simultaneously. Based on the derived components, an individual sliding window approach (44 s window) and a subsequent k-means clustering were conducted separately for each cohort to derive dFC states (reemerging intra- and interindividual connectivity patterns). From these states, we derived temporal metrics, such as average dwell time per state, state attendance, and number of transitions and compared them between groups and cohorts. Further, we correlated these with the respective measures for local dopaminergic impairment and clinical severity. The cohorts did not differ regarding age and sex. Between cohorts, PD groups differed regarding disease duration, education, cognitive scores and L-dopa equivalent daily dose. In both cohorts, the dFC analysis resulted in three distinct states, varying in connectivity patterns and strength. In the PPMI cohort, PD patients showed a lower state attendance for the globally integrated (GI) state and a lower number of transitions than controls. Significantly, worse motor scores (Unified Parkinson's Disease Rating Scale Part III) and dopaminergic impairment in the putamen and the caudate were associated with low average dwell time in the GI state and a low total number of transitions. These results were not observed in the KFO cohort: No group differences in dFC measures or associations between dFC variables and dopamine synthesis capacity were observed. Notably, worse motor performance was associated with a low number of bidirectional transitions between the GI and the lesser connected (LC) state across the PD groups of both cohorts. Hence, in early PD, relative preservation of motor performance may be linked to a more dynamic engagement of an interconnected brain state. Specifically, those large-scale network dynamics seem to relate to striatal dopamine availability. Notably, most of these results were obtained only for one cohort, suggesting that dFC is impacted by certain cohort features like educational level, or disease severity. As we could not pinpoint these features with the data at hand, we suspect that other, in our case untracked, demographical features drive connectivity dynamics in PD. PRACTITIONER POINTS: Exploring dopamine's role in brain network dynamics in two Parkinson's disease (PD) cohorts, we unraveled PD-specific changes in dynamic functional connectivity. Results in the Parkinson's Progression Marker Initiative (PPMI) and the KFO cohort suggest motor performance may be linked to a more dynamic engagement and disengagement of an interconnected brain state. Results only in the PPMI cohort suggest striatal dopamine availability influences large-scale network dynamics that are relevant in motor control.

Dynamic functional connectivity is modulated by the amount of p-Tau231 in blood in cognitively intact participants.

Electrophysiology and plasma biomarkers are early and non-invasive candidates for Alzheimer's disease detection. The purpose of this paper is to evaluate changes in dynamic functional connectivity measured with magnetoencephalography, associated with the plasma pathology marker p-tau231 in unimpaired adults. 73 individuals were included. Static and dynamic functional connectivity were calculated using leakage corrected amplitude envelope correlation. Each source's strength entropy across trials was calculated. A data-driven statistical analysis was performed to find the association between functional connectivity and plasma p-tau231 levels. Regression models were used to assess the influence of other variables over the clusters' connectivity. Frontotemporal dynamic connectivity positively associated with p-tau231 levels. Linear regression models identified pathological, functional and structural factors that influence dynamic functional connectivity. These results expand previous literature on dynamic functional connectivity in healthy individuals at risk of AD, highlighting its usefulness as an early, non-invasive and more sensitive biomarker.

Time-varying functional connectivity predicts fluctuations in sustained attention in a serial tapping task.

The mechanisms for how large-scale brain networks contribute to sustained attention are unknown. Attention fluctuates from moment to moment, and this continuous change is consistent with dynamic changes in functional connectivity between brain networks involved in the internal and external allocation of attention. In this study, we investigated how brain network activity varied across different levels of attentional focus (i.e., "zones"). Participants performed a finger-tapping task, and guided by previous research, in-the-zone performance or state was identified by low reaction time variability and out-of-the-zone as the inverse. In-the-zone sessions tended to occur earlier in the session than out-of-the-zone blocks. This is unsurprising given the way attention fluctuates over time. Employing a novel method of time-varying functional connectivity, called the quasi-periodic pattern analysis (i.e., reliable, network-level low-frequency fluctuations), we found that the activity between the default mode network (DMN) and task positive network (TPN) is significantly more anti-correlated during in-the-zone states versus out-of-the-zone states. Furthermore, it is the frontoparietal control network (FPCN) switch that differentiates the two zone states. Activity in the dorsal attention network (DAN) and DMN were desynchronized across both zone states. During out-of-the-zone periods, FPCN synchronized with DMN, while during in-the-zone periods, FPCN switched to synchronized with DAN. In contrast, the ventral attention network (VAN) synchronized more closely with DMN during in-the-zone periods compared with out-of-the-zone periods. These findings demonstrate that time-varying functional connectivity of low frequency fluctuations across different brain networks varies with fluctuations in sustained attention or other processes that change over time.

The role of the thalamic subregions in major depressive disorder with childhood maltreatment: Evidences from dynamic and static functional connectivity

BackgroundMajor depressive disorder (MDD) with a history of childhood maltreatment represents a highly prevalent clinical phenotype. Previous studies have demonstrated functional alterations of the thalamus among MDD. However, no study has investigated the static and dynamic changes in functional connectivity (FC) within thalamic subregions among MDD with childhood maltreatment. MethodsThis study included four groups: MDD with childhood maltreatment (n = 48), MDD without childhood maltreatment (n = 30), healthy controls with childhood maltreatment (n = 57), and healthy controls without childhood maltreatment (n = 46). Sixteen thalamic subregions were selected as seed to investigate group-differences in dynamic FC (dFC) and static FC (sFC). Correlation analyses were performed to assess the associations between abnormal FC and maltreatment severity. Eventually, moderation analyses were employed to explore the moderating role of abnormal FC in the relationship between maltreatment and depressive severity. ResultsMDD with childhood maltreatment exhibit abnormal thalamic subregions FC compared to MDD without childhood maltreatment, characterized by abnormalities with the sFC of the rostral anterior cingulate cortex, with the dFC of the calcarine, middle cingulate cortex, precuneus cortex and superior temporal gyrus. Furthermore, sFC with the rostral anterior cingulate cortex and dFC with the middle cingulate cortex were correlated with the severity of maltreatment. Additionally, dFC with the superior temporal gyrus moderates the relationship between maltreatment and depression severity. LimitationsThe cross-sectional designs fail to infer causality. ConclusionsOur findings support thalamic dysfunction as neurobiological features of childhood maltreatment as well as vulnerability to MDD.

Dynamic functional connectivity changes associated with psychiatric traits and cognitive deficits in Cushing’s disease

Cushing’s disease is a rare neuroendocrine disorder with excessive endogenous cortisol, impaired cognition, and psychiatric symptoms. Evidence from resting-state fMRI revealed the abnormalities of static brain connectivity in patients with Cushing’s disease (CD patients). However, it is unknown whether the CD patients’ dynamic functional connectivity would be abnormal and whether the dynamic features are associated with deficits in cognition and psychopathological symptoms. Here, we evaluated 50 patients with Cushing’s disease and 57 healthy participants by using resting-state fMRI and dynamic functional connectivity (dFNC) approach. We focused on the dynamic features of default mode network (DMN), salience network (SN), and central executive network (CEN) because these are binding sites for the cognitive-affective process, as well as vital in understanding the pathophysiology of psychiatric disorders. The dFNC was further clustered into four states by k-mean clustering. CD patients showed more dwell time in State 1 but less time in State 4. Intriguingly, group differences in dwell time in these two states can explain the cognitive deficits of CD patients. Moreover, the inter-network connections between DMN and SN and the engagement time in State 4 negatively correlated with anxiety and depression but positively correlated with cognitive performance. Finally, the classifier trained by the dynamic features of these networks successfully classified CD patients from healthy participants. Together, our study revealed the dynamic features of CD patients’ brains and found their associations with impaired cognition and emotional symptoms, which may open new avenues for understanding the cognitive and affective deficits induced by Cushing’s disease.

Dynamic functional connectivity changes associated with decreased memory performance in betel quid dependence.

The temporal variability of the dynamic functional connectivity (dFC) has been suggested as a useful metric for studying abnormal cognitive function. This study aimed to explore the associations between the temporal properties of dFC and memory performance in betel quid dependence (BQD). Sixty-four BQD individuals and 47 gender- and age-matched healthy controls (HCs) underwent functional magnetic resonance imaging and a series of neuropsychological assessments. The dFC was constructed by calculating the Pearson correlation coefficients within a sliding window and was clustered into three functional connectivity states using k-means clustering. The dFC temporal properties derived from the cluster results were compared between the BQD and HC groups. The results showed that States 1 and 3 featured more frequent and weak connectivity, and State 2 featured less frequent and strong connectivity. There were significant differences for mean dwell time (MDT) in State 3 (p = 0.022) and fraction of time in State 2 (p = 0.018) between the BQD and HC groups. Pearson correlation analyses showed that the MDT in State 1 was negatively correlated with long delay free recall and short delay free recall, and the MDT in State 3 was positively correlated with false positive of long delay recall. Our findings provide strong evidence that MDT match the memory performance and suggest new insights into the pathophysiological mechanism of memory disorders in BQD individuals.

Dynamic Dysregulation of the Triple Network of the Brain in Mild Traumatic Brain Injury and Its Relationship With Cognitive Performance.

A triple network model consisting of a default network, a salience network, and a central executive network has recently been used to understand connectivity patterns in cognitively normal versus dysfunctional brains. This study aimed to explore changes in the dynamic connectivity of triplet network in mild traumatic brain injury (mTBI) and its relationship to cognitive performance. In this work, we acquired resting-state functional magnetic resonance imaging (fMRI) data from 30 mTBI patients and 30 healthy controls (HCs). Independent component analysis, sliding time window correlation, and k-means clustering were applied to resting-state fMRI data. Further, we analyzed the relationship between changes in dynamic functional connectivity (FC) parameters and clinical variables in mTBI patients. The results showed that the dynamic functional connectivity of the brain triple network was clustered into five states. Compared with HC, mTBI patients spent longer in state 1, which is characterized by weakened dorsal default mode network (DMN) and anterior salience network (SN) connectivity, and state 3, which is characterized by a positive correlation between DMN and SN internal connectivity. Mild TBI patients had fewer metastases in different states than HC patients. In addition, the mean residence time in state 1 correlated with Montreal Cognitive Assessment scores in mTBI patients; the number of transitions between states correlated with Glasgow Coma Score in mTBI patients. Taken together, our findings suggest that the dynamic properties of FC in the triple network of mTBI patients are abnormal, and provide a new perspective on the pathophysiological mechanism of cognitive impairment from the perspective of dynamic FC.

N°221 – Changes in dynamic functional connectivity in prodromal dementia with Lewy body

N°221 – Changes in dynamic functional connectivity in prodromal dementia with Lewy body

113. Static and Dynamic Functional Connectivity Changes From the Lateral Habenula Associate With Therapeutic Response to Ketamine Treatment in Major Depression

113. Static and Dynamic Functional Connectivity Changes From the Lateral Habenula Associate With Therapeutic Response to Ketamine Treatment in Major Depression

Abnormal dynamic functional connectivity changes correlated with non-motor symptoms of Parkinson's disease.

Non-motor symptoms are common in Parkinson's disease (PD) patients, decreasing quality of life and having no specific treatments. This research investigates dynamic functional connectivity (FC) changes during PD duration and its correlations with non-motor symptoms. Twenty PD patients and 19 healthy controls (HC) from PPMI dataset were collected and used in this study. Independent component analysis (ICA) was performed to select significant components from the entire brain. Components were grouped into seven resting-state intrinsic networks. Static and dynamic FC changes during resting-state functional magnetic resonance imaging (fMRI) were calculated based on selected components and resting state networks (RSN). Static FC analysis results showed that there was no difference between PD-baseline (PD-BL) and HC group. Network averaged connection between frontoparietal network and sensorimotor network (SMN) of PD-follow up (PD-FU) was lower than PD-BL. Dynamic FC analysis results suggested four distinct states, and each state's temporal characteristics, such as fractional windows and mean dwell time, were calculated. The state 2 of our study showed positive coupling within and between SMN and visual network, while the state 3 showed hypo-coupling through all RSN. The fractional windows and mean dwell time of PD-FU state 2 (positive coupling state) were statistically lower than PD-BL. Fractional windows and mean dwell time of PD-FU state 3 (hypo-coupling state) were statistically higher than PD-BL. Outcome scales in Parkinson's disease-autonomic dysfunction scores of PD-FU positively correlated with mean dwell time of state 3 of PD-FU. Overall, our finding indicated that PD-FU patients spent more time in hypo-coupling state than PD-BL. The increase of hypo-coupling state and decrease of positive coupling state might correlate with the worsening of non-motor symptoms in PD patients. Dynamic FC analysis of resting-state fMRI can be used as monitoring tool for PD progression.

Altered dynamic functional connectivity in the primary visual cortex in patients with primary angle-closure glaucoma.

Glaucoma is the main blindness-causing disease in the world. Previous neuroimaging studies demonstrated that glaucoma not only causes the loss of optic ganglion cells but also leads to the abnormal function of the optic nerve pathway and the visual cortex. However, previous studies also reported that patients with glaucoma have dysfunction in the visual cortex in a static state. Whether or not patients with primary angle-closure glaucoma (PACG) were accompanied by dynamic functional connectivity (FC) changes in the primary visual cortex (V1) remains unknown. A total of 34 patients with PACG (23 men and 11 women) and 34 well-matched healthy controls (HCs) were enrolled in the study. The dynamic functional connectivity (dFC) with the sliding window method was applied to investigate the dynamic functional connectivity changes in the V1. Compared with HCs, patients with PACG showed increased dFC values between left V1 and bilateral calcarine (CAL). Meanwhile, patients with PACG showed increased dFC values between right V1 and bilateral CAL. Our study demonstrated that patients with PACG showed increased dFC within the visual network, which might indicate the increased variability FC in the V1 in patients with PACG.

Age-dependent changes in the dynamic functional organization of the brain at rest: a cross-cultural replication approach.

Age-associated changes in brain function play an important role in the development of neurodegenerative diseases. Although previous work has examined age-related changes in static functional connectivity, accumulating evidence suggests that advancing age is especially associated with alterations in the dynamic interactions and transitions between different brain states, which hitherto have received less attention. Conclusions of previous studies in this domain are moreover limited by suboptimal replicability of resting-state functional magnetic resonance imaging (fMRI) and culturally homogenous cohorts. Here, we investigate the robustness of age-associated changes in dynamic functional connectivity (dFC) by capitalizing on the availability of fMRI cohorts from two cultures (Western European and Chinese). In both the LEMON (Western European) and SALD (Chinese) cohorts, we consistently identify two distinct states: a more frequent segregated within-network connectivity state (state I) and a less frequent integrated between-network connectivity state (state II). Moreover, in both these cohorts, older (55-80years) compared to younger participants (20-35years) exhibited lower occurrence of and spent less time in state I. Older participants also tended to exhibit more transitions between networks and greater variance in global efficiency. Overall, our cross-cultural replication of age-associated changes in dFC metrics implies that advancing age is robustly associated with a reorganization of dynamic brain activation that favors the use of less functionally specific networks.

More than static: altered dynamic functional connectivity of primary visual cortex in the comitant exotropia patients.

Previous neuroimaging studies have demonstrated that comitant exotropia (CE) patients exhibit dysfunction in various visual cortical areas. However, whether the CE patients showed abnormal dynamic functional connectivity (dFC) in primary visual cortex (V1) changes remains unknown. A total of 36 CE patients (25 males and 11 females) and 36 well-matched healthy control subjects (HCs) were enrolled in the study. The dFC with sliding window method was applied to investigate the dynamic functional connectivity changes in primary visual cortex (V1). Compared with HCs, CE patients had decreased dFC values between left V1 and right fusiform (Fus), right lingual (LING), left orbital medial frontal gyrus, left Fus, left calcarine and left precuneus (PreCUN). Meanwhile, CE patients had decreased dFC values between right V1 and left cerebelum_6 (CER_6), right lingual and left inferior occipital gyrus. Our study demonstrates that CE patients showed altered dFC within visual network and V1-default mode network, which might indicate the decreased variability FC values in the primary visual cortex in CE patients.

Use of connectotyping on task functional MRI data reveals dynamic network level cross talking during task performance

Task-based functional MRI (fMRI) has greatly improved understanding of brain functioning, enabling the identification of brain areas associated with specific cognitive operations. Traditional analyses are limited to associating activation patterns in particular regions with specific cognitive operation, largely ignoring regional cross-talk or dynamic connectivity, which we propose is crucial for characterization of brain function in the context of task fMRI. We use connectotyping, which efficiently models functional brain connectivity to reveal the progression of temporal brain connectivity patterns in task fMRI. Connectotyping was employed on data from twenty-four participants (12 male, mean age 24.8 years, 2.57 std. dev) who performed a widely spaced event-related fMRI word vs. pseudoword decision task, where stimuli were presented every 20 s. After filtering for movement, we ended up with 15 participants that completed each trial and had enough usable data for our analyses. Connectivity matrices were calculated per participant across time for each stimuli type. A Repeated Measures ANOVA applied on the connectotypes was used to characterize differences across time for words and pseudowords. Our group level analyses found significantly different dynamic connectivity patterns during word vs. pseudoword processing between the Fronto-Parietal and Cingulo-Parietal Systems, areas involved in cognitive task control, memory retrieval, and semantic processing. Our findings support the presence of dynamic changes in functional connectivity during task execution and that such changes can be characterized using connectotyping but not with traditional Pearson’s correlations.

Dynamic functional connectivity changes of resting-state brain network in attention-deficit/hyperactivity disorder

Patients with attention-deficit/hyperactivity disorder (ADHD) have shown abnormal functional connectivity and network disruptions at the whole-brain static level. However, the changes in brain networks in ADHD patients from dynamic functional connectivity (DFC) perspective have not been fully understood. Accordingly, we executed DFC analysis on resting-state fMRI data of 25 ADHD patients and 27 typically developing (TD) children. A sliding window and Pearson correlation were used to construct the dynamic brain network of all subjects. The k-means+ + clustering method was used to recognize three recurring DFC states, and finally, the mean dwell time, the fraction of time spent for each state, and graph theory metrics were quantified for further analysis. Our results showed that ADHD patients had abnormally increased mean dwell time and the fraction of time spent in state 2, which reached a significant level (p < 0.05). In addition, a weak correlation between the default mode network was associated in three states, and the positive correlations between visual network and attention network were smaller than TD in three states. Finally, the integration of each network node of ADHD in state 2 is more potent than that of TD, and the degree of node segregation is smaller than that of TD. These findings provide new evidence for the DFC study of ADHD; dynamic changes may better explain the developmental delay of ADHD and have particular significance for studying neurological mechanisms and adjuvant therapy of ADHD.

Dynamic Functional Connectivity of Emotion Processing in Beta Band with Naturalistic Emotion Stimuli.

While naturalistic stimuli, such as movies, better represent the complexity of the real world and are perhaps crucial to understanding the dynamics of emotion processing, there is limited research on emotions with naturalistic stimuli. There is a need to understand the temporal dynamics of emotion processing and their relationship to different dimensions of emotion experience. In addition, there is a need to understand the dynamics of functional connectivity underlying different emotional experiences that occur during or prior to such experiences. To address these questions, we recorded the EEG of participants and asked them to mark the temporal location of their emotional experience as they watched a video. We also obtained self-assessment ratings for emotional multimedia stimuli. We calculated dynamic functional the connectivity (DFC) patterns in all the frequency bands, including information about hubs in the network. The change in functional networks was quantified in terms of temporal variability, which was then used in regression analysis to evaluate whether temporal variability in DFC (tvDFC) could predict different dimensions of emotional experience. We observed that the connectivity patterns in the upper beta band could differentiate emotion categories better during or prior to the reported emotional experience. The temporal variability in functional connectivity dynamics is primarily related to emotional arousal followed by dominance. The hubs in the functional networks were found across the right frontal and bilateral parietal lobes, which have been reported to facilitate affect, interoception, action, and memory-related processing. Since our study was performed with naturalistic real-life resembling emotional videos, the study contributes significantly to understanding the dynamics of emotion processing. The results support constructivist theories of emotional experience and show that changes in dynamic functional connectivity can predict aspects of our emotional experience.

Temporal-spatial dynamic functional connectivity analysis in schizophrenia classification.

With the development of resting-state functional magnetic resonance imaging (rs-fMRI) technology, the functional connectivity network (FCN) which reflects the statistical similarity of temporal activity between brain regions has shown promising results for the identification of neuropsychiatric disorders. Alteration in FCN is believed to have the potential to locate biomarkers for classifying or predicting schizophrenia (SZ) from healthy control. However, the traditional FCN analysis with stationary assumption, i.e., static functional connectivity network (SFCN) at the time only measures the simple functional connectivity among brain regions, ignoring the dynamic changes of functional connectivity and the high-order dynamic interactions. In this article, the dynamic functional connectivity network (DFCN) is constructed to delineate the characteristic of connectivity variation across time. A high-order functional connectivity network (HFCN) designed based on DFCN, could characterize more complex spatial interactions across multiple brain regions with the potential to reflect complex functional segregation and integration. Specifically, the temporal variability and the high-order network topology features, which characterize the brain FCNs from region and connectivity aspects, are extracted from DFCN and HFCN, respectively. Experiment results on SZ identification prove that our method is more effective (i.e., obtaining a significantly higher classification accuracy, 81.82%) than other competing methods. Post hoc inspection of the informative features in the individualized classification task further could serve as the potential biomarkers for identifying associated aberrant connectivity in SZ.

White matter substrates of functional connectivity dynamics in the human brain

The contribution of structural connectivity to functional connectivity dynamics is still far from being elucidated. Herein, we applied track-weighted dynamic functional connectivity (tw-dFC), a model integrating structural, functional, and dynamic connectivity, on high quality diffusion weighted imaging and resting-state fMRI data from two independent repositories. The tw-dFC maps were analyzed using independent component analysis, aiming at identifying spatially independent white matter components which support dynamic changes in functional connectivity. Each component consisted of a spatial map of white matter bundles that show consistent fluctuations in functional connectivity at their endpoints, and a time course representative of such functional activity. These components show high intra-subject, inter-subject, and inter-cohort reproducibility. We provided also converging evidence that functional information about white matter activity derived by this method can capture biologically meaningful features of brain connectivity organization, as well as predict higher-order cognitive performance.

Temporal Dynamics of Resting-state Functional Networks and Cognitive Functioning following Systemic Treatment for Breast Cancer

Many women with breast cancer suffer from a decline in memory and executive function, particularly after treatment with chemotherapy. Recent neuroimaging studies suggest that changes in network dynamics are fundamental in decline in these cognitive functions. This has, however, not yet been investigated in breast cancer patients. Using resting state functional magnetic resonance imaging, we prospectively investigated whether changes in dynamic functional connectivity were associated with changes in memory and executive function. We examined 34 breast cancer patients that received chemotherapy, 32 patients that did not receive chemotherapy, and 35 no-cancer controls. All participants were assessed prior to treatment and six months after completion of chemotherapy, or at similar intervals for the other groups. To assess memory and executive function, we used the Hopkins Verbal Learning Test – Immediate Recall and the Trail Making Test B, respectively. Using a sliding window approach, we then evaluated dynamic functional connectivity of resting state networks supporting memory and executive function, i.e. the default mode network and frontoparietal network, respectively. Next, we directly investigated the association between cognitive performance and dynamic functional connectivity. We found no group differences in cognitive performance or connectivity measures. The association between dynamic functional connectivity of the default mode network and memory differed significantly across groups. This was not the case for the frontoparietal network and executive function. This suggests that cancer and chemotherapy alter the role of dynamic functional connectivity in memory function. Further implications of these findings are discussed.

This Month in Anesthesiology

This Month in Anesthesiology