Effective Connectivity Analysis Research Articles

Processing demands modulate the activities and functional connectivity patterns of the posterior (VWFA-1) and anterior (VWFA-2) VWFA

Previous studies have shown that the visual word form area (VWFA) has structural and intrinsic functional connectivity with both language and attention networks. Nevertheless, it is still unclear how the functional connectivity pattern of the VWFA is regulated by processing demands induced by experimental tasks, and whether processing demands differentially regulate the posterior (VWFA-1) and anterior (VWFA-2) subregions of the VWFA. To address these questions, the present study adopted two tasks varying in processing demands (i.e., verbal and non-verbal tasks), and used generalized psychophysiological interaction (gPPI) and dynamic causal modeling (DCM) analyses to explore the task-dependent functional connectivity patterns of the two subregions of the VWFA. Activation analysis revealed that the VWFA-2 showed higher activation for the verbal task than the non-verbal task, while there were no activation differences in the VWFA-1 after controlling for the stimulus driven effects. Functional and effective connectivity analyses revealed that, for both VWFA-1 and VWFA-2, the verbal task enhanced connections from VWFAs to the ventral language regions (e.g., the left orbital frontal cortex), while the non-verbal task enhanced connections from VWFAs to the dorsal visuospatial regions (e.g., the left intraparietal sulcus). Results of the present study indicate that processing demands induced by tasks modulate both the local activity and functional connectivity patterns of the VWFA, providing new insights for understanding its domain-general function.

Selective Brain Activations and Connectivities Related to the Storage and Recall of Human Object-Location, Reward-Location, and Word-Pair Episodic Memories.

Different cortical systems to the hippocampus were activated using fMRI during different types of episodic memory task. For object with scene location episodic memory, the activations were high in cortical systems involved in spatial processing, including the ventromedial visual and medial parahippocampal system. These activations for the medial parahippocampal system were higher in the right hemisphere. The activations in the face and object processing ventrolateral visual cortical stream regions FFC, PIT, V8 and TE2p were higher in the object-location in scene task than the reward-location task, and were higher in the right hemisphere. For reward-location in scene episodic memory, activations were also high in the ventromedial visual cortical spatial stream to the hippocampus, but were also selectively high in storage in key reward cortical regions (ventromedial prefrontal 10r, 10v, 10d; pregenual anterior cingulate d32, p24, p32, s32; and medial orbitofrontal cortex reward-related pOFC, 11l, OFC). For word-pair episodic memory, activations were lower in the ventromedial visual and medial parahippocampal spatial cortical stream, and were higher in language-related regions in Broca's area (44, 45, 47l), and were higher in the left hemisphere for these regions and for the many highly connected inferior frontal gyrus regions in the left hemisphere. Further, effective connectivity analyses during the episodic memory tasks showed that the direction of connectivity for these systems was from early visual cortical regions V2-V4 to the ventromedial visual cortical regions VMV1-3 and VVC for spatial scene processing; was from the pregenual anterior cingulate and orbitofrontal cortex reward systems to the hippocampal system; and was from the FFC/V8/PIT system to TE2p in the visual inferior temporal visual cortex, which has connectivity to lateral parahippocampal TF, which in turn has forward effective connectivity to the hippocampus.

A novel brain network analysis method for pediatric ADHD using RFE-GA feature selection strategy

Attention Deficit Hyperactivity Disorder (ADHD) is a highly prevalent childhood disorder, and related research has been increasing in recent years. However, it remains a challenging issue to accurately identify individuals with ADHD. The research proposes a method for ADHD detection using Recursive Feature Elimination-Genetic Algorithm (RFE-GA) for the feature selection of EEG data. Firstly, this study employed Transfer Entropy (TE) to construct brain networks from the EEG data of the ADHD and Normal groups, conducting an analysis of effective connectivity to unveil causal relationships in the brain's information exchange activities. Subsequently, a dual-layer feature selection method combining Recursive Feature Elimination (RFE) and Genetic Algorithm (GA) was proposed. Using the global search capability of GA and the feature selection ability of RFE, the performance of each feature subset is evaluated to find the optimal feature subset. Finally, a Support Vector Machine (SVM) classifier was employed to classify the ultimate feature set. The results revealed the control group exhibited lower connectivity strength in the left temporal alpha and beta bands, but higher frontal connectivity strength compared to the ADHD group. Additionally, in the gamma frequency band, the control group had higher top lobe connectivity strength than the ADHD group. Through the RFE-GA feature selection method, the optimized feature set was more concise, achieving classification accuracies of 91.3%, 94.1%, and 90.7% for the alpha, beta, and gamma frequency bands, respectively. The proposed RFE-GA feature selection method significantly reduced the number of features, thereby improving classification accuracy.&#xD.

Action expectancy modulates activity in the mirror neuron system and mentalizing system

Action understanding involves two distinct processing levels that engage separate neural mechanisms: perception of concrete kinematic information and recognition of abstract action intentions. The mirror neuron system and the mentalizing system have both been linked to concrete action and abstract information processing, but their specific roles remain debatable. Here, we conducted a functional magnetic resonance imaging study with 26 participants who passively observed expected and unexpected actions. We performed whole-brain activation, region of interest, and effective connectivity analyses to investigate the neural correlates of these actions. Whole-brain activation analyses revealed that expected actions were associated with increased activation in the left medial superior frontal gyrus, while unexpected actions were linked to heightened activity in the left supramarginal gyrus, left superior parietal lobule, right inferior temporal gyrus, and left middle frontal gyrus. Region of interest analyses demonstrated that the left ventral premotor cortex exhibited greater activation during the observation of expected actions compared to unexpected actions, while the left inferior frontal gyrus, left superior parietal lobule, and left precuneus showed stronger activation during the observation of unexpected actions. Effective connectivity was observed between the left ventral premotor cortex and the left angular gyrus, left intraparietal sulcus, left dorsal premotor cortex, and left ventromedial prefrontal cortex with the middle frontal gyrus when observing unexpected, but not expected, actions. These findings suggest that expected actions are primarily processed by the mirror neuron system, whereas unexpected actions engage both the mirror neuron system and the mentalizing system, with these systems playing complementary roles in the understanding of unexpected actions.

InfoFlowNet: A multi-head attention-based self-supervised learning model with surrogate approach for uncovering brain effective connectivity

Deciphering brain network topology can enhance the depth of neuroscientific knowledge and facilitate the development of neural engineering methods. Effective connectivity, which gauges the directional influences among brain regions, is pivotal for these studies. This research introduces InfoFlowNet, a novel self-supervised learning model designed to infer causal relationships in electroencephalogram (EEG) data, aiming at capturing the complex information flow among brain regions. Specifically, InfoFlowNet employs convolution operations and multi-head self-attention mechanisms with a masking feature, which ignores self-connections to focus on inter-regional dynamics. Additionally, a new causal magnitude estimation is introduced by assessing the impact of shuffled surrogate data on signal prediction to quantify causal influence. Experiments using synthetic data and real EEG datasets demonstrate that InfoFlowNet effectively uncovers time-varying causal relationships. Compared with the Granger causality model (GCM) and the temporal causal discovery framework (TCDF), InfoFlowNet shows superior sensitivity in detecting significant causal edges. For instance, in a psychomotor vigilance task, InfoFlowNet identified 8 out of 16 significant causal edges, significantly outperforming GCM and TCDF. Furthermore, InfoFlowNet successfully passes the whiteness test on the model's residuals, and advanced analyses illustrate the advantages of utilizing multi-head attention and masking mechanisms to capture effective connectivity. In sum, InfoFlowNet represents a significant advancement in the analysis of effective connectivity, offering a deeper understanding of brain network dynamics. The model's ability to discern complex causal interactions supports its potential application in broader neuroscientific research and applications.

Ictal-onset localization through effective connectivity analysis based on RNN-GC with intracranial EEG signals in patients with epilepsy

Epilepsy is one of the most common clinical diseases of the nervous system. The occurrence of epilepsy will bring many serious consequences, and some patients with epilepsy will develop drug-resistant epilepsy. Surgery is an effective means to treat this kind of patients, and lesion localization can provide a basis for surgery. The purpose of this study was to explore the functional types and connectivity evolution patterns of relevant regions of the brain during seizures. We used intracranial EEG signals from patients with epilepsy as the research object, and the method used was GRU-GC. The role of the corresponding area of each channel in the seizure process was determined by the introduction of group analysis. The importance of each area was analysed by introducing the betweenness centrality and PageRank centrality. The experimental results show that the classification method based on effective connectivity has high accuracy, and the role of the different regions of the brain could also change during the seizures. The relevant methods in this study have played an important role in preoperative assessment and revealing the functional evolution patterns of various relevant regions of the brain during seizures.

Retention of verbal and nonverbal information in the working memory. An analysis of functional and effective connectivity

In this work we estimated differences in the structure of brain systems that ensure encoding and retention in working memory (WM) of two types of information: verbal (letters) and non-verbal (segments of an open broken line) sequences presented either statically or dynamically. Brain systems were characterized by the strength of functional and effective connections between eight approximately bilaterally symmetrical cortical loci, including the dorsolateral prefrontal cortex (dlPFC) and regions of the temporal (STG), parietal (IPS), and occipital (v2) cortices. Using an 8-channel vector autoregressive model in the space of cortical EEG sources, it was shown in a group of subjects in whom high-density EEG was recorded that: (1) the brain organization of the WM when holding a sequence of letters differs from that when holding a sequence of broken line segments; (2) the brain organization of the WM depends on the mode of presentation of sequences: the strength of the functional connection is different during dynamic and static presentation of the sequence; (3) differences in the structure of functional and effective connections are not of a pronounced frequency-selective nature and are observed in all studied EEG frequency ranges from theta (4–8 Hz) to high-frequency gamma (50–60 Hz); (4) the most reliable differences between the task of retaining a sequence of letters and the task of retaining a sequence of broken line segments are observed in the alpha and beta frequency ranges during static visual presentation of sequences in the strength of functional connectivity measured using coherence between the left hemisphere dlPFC and the right hemisphere STG, as well as in theta range between the right hemisphere dlPFC and the left visual cortex v2; (5) the most reliable difference between static and dynamic presentation modes is observed in the task of holding broken line segments in the gamma frequency range (50–60 Hz) between the dlPFC in the right hemisphere and the left visual cortex v2.

NHSMM-MAR-sdNC: A novel data-driven computational framework for state-dependent effective connectivity analysis

The brain exhibits intrinsic dynamics characterized by spontaneous spatiotemporal reorganization of neural activity or metastability, which is associated closely with functional integration and segregation. Compared to dynamic functional connectivity, state-dependent effective connectivity (i.e., dynamic effective connectivity) is more suitable for exploring the metastability as its ability to infer causalities between brain regions. However, methods for state-dependent effective connectivity are scarce and urgently needed. In this study, a novel data-driven computational framework, named NHSMM-MAR-sdNC integrating nonparametric hidden semi-Markov model combined with multivariate autoregressive model and state-dependent new causality, is proposed to investigate the state-dependent effective connectivity. The framework is not constrained by any biological assumptions. Furthermore, state number can be inferred from the observed data directly and the state duration distributions will be estimated explicitly rather than restricted by geometric form, which overcomes limitations of hidden Markov model. Experimental results of synthetic data show that the framework can identify the state number adaptively and the state-dependent causality networks accurately. The dynamics of state-related causality networks are also revealed by the new method on real-world resting-state fMRI data. Our method provides a new data-driven computational framework for identifying state-dependent effective connectivity, which will facilitate the identification and assessment of metastability and itinerant dynamics of the brain.

Speech and neuroimaging effects following HiCommunication: a randomized controlled group intervention trial in Parkinson's disease.

Speech, voice and communication changes are common in Parkinson's disease. HiCommunication is a novel group intervention for speech and communication in Parkinson's disease based on principles driving neuroplasticity. In a randomized controlled trial, 95 participants with Parkinson's disease were allocated to HiCommunication or an active control intervention. Acoustic analysis was performed pre-, post- and six months after intervention. Intention-to-treat analyses with missing values imputed in linear multilevel models and complimentary per-protocol analyses were performed. The proportion of participants with a clinically relevant increase in the primary outcome measure of voice sound level was calculated. Resting-state functional MRI was performed pre- and post-intervention. Spectral dynamic causal modelling and the parametric empirical Bayes methods were applied to resting-state functional MRI data to describe effective connectivity changes in a speech-motor-related network of brain regions. From pre- to post-intervention, there were significant group-by-time interaction effects for the measures voice sound level in text reading (unstandardized b = 2.3, P = 0.003), voice sound level in monologue (unstandardized b = 2.1, P = 0.009), Acoustic Voice Quality Index (unstandardized b = -0.5, P = 0.016) and Harmonics-to-Noise Ratio (unstandardized b = 1.3, P = 0.014) post-intervention. For 59% of the participants, the increase in voice sound level after HiCommunication was clinically relevant. There were no sustained effects at the six-month follow-up. In the effective connectivity analysis, there was a significant decrease in inhibitory self-connectivity in the left supplementary motor area and increased connectivity from the right supplementary motor area to the left paracentral gyrus after HiCommunication compared to after the active control intervention. In conclusion, the HiCommunication intervention showed promising effects on voice sound level and voice quality in people with Parkinson's disease, motivating investigations of barriers and facilitators for implementation of the intervention in healthcare settings. Resting-state brain effective connectivity was altered following the intervention in areas implicated, possibly due to reorganization in brain networks.

Functional and Effective Connectivity Underlying Semantic Verbal Fluency.

Semantic verbal fluency (SVF) impairment is present in several neurological disorders. Although activation in SVF-related areas has been reported, how these regions are connected and their functional roles in the network remain divergent. We assessed SVF static and dynamic functional connectivity (FC) and effective connectivity in healthy participants using functional magnetic resonance imaging. We observed activation in the inferior frontal (IFG), middle temporal (pMTG) and angular gyri (AG), anterior cingulate (AC), insular cortex, and regions of the superior, middle, and medial frontal gyri (SFG, MFG, MidFG). Our static FC analysis showed a highly interconnected task and resting state network. Increased connectivity of AC with the pMTG and AG was observed for the task. The dynamic FC analysis provided circuits with connections similarly modulated across time and regions related to category identification, language comprehension, word selection and recovery, word generation, inhibition of speaking, speech planning, and articulatory planning of orofacial movements. Finally, the effective connectivity analysis provided a network that best explained our data, starting at the AG and going to the pMTG, from which there was a division between the ventral and dorsal streams. The SFG and MFG regions were connected and modulated by the MidFG, while the inferior regions formed the ventral stream. Therefore, we successfully assessed the SVF network, exploring regions associated with the entire processing, from category identification to word generation. The methodological approach can be helpful for further investigation of the SVF network in neurological disorders.

Elucidating the underlying components of metacognitive systematic bias in the human dorsolateral prefrontal cortex and inferior parietal cortex

Metacognitive systematic bias impairs human learning efficiency, which is characterized by the inconsistency between predicted and actual memory performance. However, the underlying mechanism of metacognitive systematic bias remains unclear in existing studies. In this study, we utilized judgments of learning task in human participants to compare the neural mechanism difference in metacognitive systematic bias. Participants encoded words in fMRI sessions that would be tested later. Immediately after encoding each item, participants predicted how likely they would remember it. Multivariate analyses on fMRI data demonstrated that working memory and uncertainty decisions are represented in patterns of neural activity in metacognitive systematic bias. The available information participants used led to overestimated bias and underestimated bias. Effective connectivity analyses further indicate that information about the metacognitive systematic bias is represented in the dorsolateral prefrontal cortex and inferior parietal cortex. Different neural patterns were found underlying overestimated bias and underestimated bias. Specifically, connectivity regions with the dorsolateral prefrontal cortex, anterior cingulate cortex, and supramarginal gyrus form overestimated bias, while less regional connectivity forms underestimated bias. These findings provide a mechanistic account for the construction of metacognitive systematic bias.

Neural representation of phonological wordform in temporal cortex.

While the neural bases of the earliest stages of speech categorization have been widely explored using neural decoding methods, there is still a lack of consensus on questions as basic as how wordforms are represented and in what way this word-level representation influences downstream processing in the brain. Isolating and localizing the neural representations of wordform is challenging because spoken words activate a variety of representations (e.g., segmental, semantic, articulatory) in addition to form-based representations. We addressed these challenges through a novel integrated neural decoding and effective connectivity design using region of interest (ROI)-based, source-reconstructed magnetoencephalography/electroencephalography (MEG/EEG) data collected during a lexical decision task. To identify wordform representations, we trained classifiers on words and nonwords from different phonological neighborhoods and then tested the classifiers' ability to discriminate between untrained target words that overlapped phonologically with the trained items. Training with word neighbors supported significantly better decoding than training with nonword neighbors in the period immediately following target presentation. Decoding regions included mostly right hemisphere regions in the posterior temporal lobe implicated in phonetic and lexical representation. Additionally, neighbors that aligned with target word beginnings (critical for word recognition) supported decoding, but equivalent phonological overlap with word codas did not, suggesting lexical mediation. Effective connectivity analyses showed a rich pattern of interaction between ROIs that support decoding based on training with lexical neighbors, especially driven by right posterior middle temporal gyrus. Collectively, these results evidence functional representation of wordforms in temporal lobes isolated from phonemic or semantic representations.

Aberrant Brain Triple-Network Effective Connectivity Patterns in Type2 Diabetes Mellitus.

Aberrant brain functional connectivity network is thought to be related to cognitive impairment in patients with type2 diabetes mellitus (T2DM). This study aims to investigate the triple-network effective connectivity patterns in patients with T2DM within and between the default mode network (DMN), salience network (SN), and executive control network (ECN) and their associations with cognitive declines. In total, 92 patients with T2DM and 98 matched healthy controls (HCs) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI). Spectral dynamic causal modeling (spDCM) was used for effective connectivity analysis within the triple network. The posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), lateral prefrontal cortex (LPFC), supramarginal gyrus (SMG), and anterior insula (AINS) were selected as the regions of interest. Group comparisons were performed for effective connectivity calculated using the fully connected model, and the relationships between effective connectivity alterations and cognitive impairment as well as clinical parameters were detected. Compared to HCs, patients with T2DM exhibited increased or decreased effective connectivity patterns within the triple network. Furthermore, diabetes duration was significantly negatively correlated with increased effective connectivity from the r-LPFC to the mPFC, while body mass index (BMI) was significantly positively correlated with increased effective connectivity from the l-LPFC to the l-AINS (r = - 0.353, p = 0.001; r = 0.377, p = 0.004). These results indicate abnormal effective connectivity patterns within the triple network model in patients with T2DM and provide new insight into the neurological mechanisms of T2DM and related cognitive dysfunction.

The influence of the precuneus on the medial temporal cortex determines the subjective quality of memory during the retrieval of naturalistic episodes.

Memory retrieval entails dynamic interactions between the medial temporal lobe and areas in the parietal and frontal cortices. Here, we tested the hypothesis that effective connectivity between the precuneus, in the medial parietal cortex, and the medial temporal cortex contributes to the subjective quality of remembering objects together with information about their rich spatio-temporal encoding context. During a 45min encoding session, the participants were presented with pictures of objects while they actively explored a virtual town. The following day, under fMRI, participants were presented with images of objects and had to report whether: they recognized the object and could remember the place/time of encoding, the object was familiar only, or the object was new. The hippocampus/parahippocampus, the precuneus and the ventro-medial prefrontal cortex activated when the participants successfully recognized objects they had seen in the virtual town and reported that they could remember the place/time of these events. Analyses of effective connectivity showed that the influence exerted by the precuneus on the medial temporal cortex mediates this effect of episodic recollection. Our findings demonstrate the role of the inter-regional connectivity in mediating the subjective experience of remembering and underline the relevance of studying memory in contextually-rich conditions.

The effective connectivity analysis of fMRI based on asymmetric detection of transfer brain entropy.

It is important to explore causal relationships in functional magnetic resonance imaging study. However, the traditional effective connectivity analysis method is easy to produce false causality, and the detection accuracy needs to be improved. In this paper, we introduce a novel functional magnetic resonance imaging effective connectivity method based on the asymmetry detection of transfer entropy, which quantifies the disparity in predictive information between forward and backward time, subsequently normalizing this disparity to establish a more precise criterion for detecting causal relationships while concurrently reducing computational complexity. Then, we evaluate the effectiveness of this method on the simulated data with different level of nonlinearity, and the results demonstrated that the proposed method outperforms others methods on the detection of both linear and nonlinear causal relationships, including Granger Causality, Partial Granger Causality, Kernel Granger Causality, Copula Granger Causality, and traditional transfer entropy. Furthermore, we applied it to study the effective connectivity of brain functional activities in seafarers. The results showed that there are significantly different causal relationships between different brain regions in seafarers compared with non-seafarers, such as Temporal lobe related to sound and auditory information processing, Hippocampus related to spatial navigation, Precuneus related to emotion processing as well as Supp_Motor_Area associated with motor control and coordination, which reflects the occupational specificity of brain function of seafarers.

Combining electrodermal activity analysis and dynamic causal modeling to investigate the visual-odor multimodal integration during face perception

Objective. This study presents a novel methodological approach for incorporating information related to the peripheral sympathetic response into the investigation of neural dynamics. Particularly, we explore how hedonic contextual olfactory stimuli influence the processing of neutral faces in terms of sympathetic response, event-related potentials and effective connectivity analysis. The objective is to investigate how the emotional valence of odors influences the cortical connectivity underlying face processing and the role of face-induced sympathetic arousal in this visual-olfactory multimodal integration. Approach. To this aim, we combine electrodermal activity (EDA) analysis and dynamic causal modeling to examine changes in cortico-cortical interactions. Results. The results reveal that stimuli arising sympathetic EDA responses are associated with a more negative N170 amplitude, which may be a marker of heightened arousal in response to faces. Hedonic odors, on the other hand, lead to a more negative N1 component and a reduced the vertex positive potential when they are unpleasant or pleasant. Concerning connectivity, unpleasant odors strengthen the forward connection from the inferior temporal gyrus (ITG) to the middle temporal gyrus, which is involved in processing changeable facial features. Conversely, the occurrence of sympathetic responses after a stimulus is correlated with an inhibition of this same connection and an enhancement of the backward connection from ITG to the fusiform face gyrus. Significance. These findings suggest that unpleasant odors may enhance the interpretation of emotional expressions and mental states, while faces capable of eliciting sympathetic arousal prioritize identity processing.

Multilevel testing of constraints induced by structural equation modeling in fMRI effective connectivity analysis: A proof of concept

In functional MRI (fMRI), effective connectivity analysis aims at inferring the causal influences that brain regions exert on one another. A common method for this type of analysis is structural equation modeling (SEM). We here propose a novel method to test the validity of a given model of structural equation. Given a structural model in the form of a directed graph, the method extracts the set of all constraints of conditional independence induced by the absence of links between pairs of regions in the model and tests for their validity in a Bayesian framework, either individually (constraint by constraint), jointly (e.g., by gathering all constraints associated with a given missing link), or globally (i.e., all constraints associated with the structural model). This approach has two main advantages. First, it only tests what is testable from observational data and does allow for false causal interpretation. Second, it makes it possible to test each constraint (or group of constraints) separately and, therefore, quantify in what measure each constraint (or, e..g., missing link) is respected in the data. We validate our approach using a simulation study and illustrate its potential benefits through the reanalysis of published data.

Alteration in temporal-cerebellar effective connectivity can effectively distinguish stable and progressive mild cognitive impairment.

Stable mild cognitive impairment (sMCI) and progressive mild cognitive impairment (pMCI) represent two distinct subtypes of mild cognitive impairment (MCI). Early and effective diagnosis and accurate differentiation between sMCI and pMCI are crucial for administering targeted early intervention and preventing cognitive decline. This study investigated the intrinsic dysconnectivity patterns in sMCI and pMCI based on degree centrality (DC) and effective connectivity (EC) analyses, with the goal of uncovering shared and distinct neuroimaging mechanisms between subtypes. Resting-state functional magnetic resonance imaging combined with DC analysis was used to explore the functional connectivity density in 42 patients with sMCI, 31 patients with pMCI, and 82 healthy control (HC) participants. Granger causality analysis was used to assess changes in EC based on the significant clusters found in DC. Furthermore, correlation analysis was conducted to examine the associations between altered DC/EC values and cognitive function. Receiver operating characteristic curve analysis was performed to determine the accuracy of abnormal DC and EC values in distinguishing sMCI from pMCI. Compared with the HC group, both pMCI and sMCI groups exhibited increased DC in the left inferior temporal gyrus (ITG), left posterior cerebellum lobe (CPL), and right cerebellum anterior lobe (CAL), along with decreased DC in the left medial frontal gyrus. Moreover, the sMCI group displayed reduced EC from the right CAL to bilateral CPL, left superior temporal gyrus, and bilateral caudate compared with HC. pMCI demonstrated elevated EC from the right CAL to left ITG, which was linked to episodic memory and executive function. Notably, the EC from the right CAL to the right ITG effectively distinguished sMCI from pMCI, with sensitivity, specificity, and accuracy of 0.5806, 0.9512, and 0.828, respectively. This study uncovered shared and distinct alterations in DC and EC between sMCI and pMCI, highlighting their involvement in cognitive function. Of particular significance are the unidirectional EC disruptions from the cerebellum to the temporal lobe, which serve as a discriminating factor between sMCI and pMCI and provide a new perspective for understanding the temporal-cerebellum. These findings offer novel insights into the neural circuit mechanisms involving the temporal-cerebellum connection in MCI.

Large-scale effective connectivity analysis reveals the existence of two mutual inhibitory systems in patients with major depression

It is posited that cognitive and affective dysfunction in patients with major depression disorder (MDD) may be caused by dysfunctional signal propagation in the brain. By leveraging dynamic causal modeling, we investigated large-scale directed signal propagation (effective connectivity) among distributed large-scale brain networks with 43 MDD patients and 56 healthy controls. The results revealed the existence of two mutual inhibitory systems: the anterior default mode network, auditory network, sensorimotor network, salience network and visual networks formed an “emotional” brain, while the posterior default mode network, central executive networks, cerebellum and dorsal attention network formed a “rational brain”. These two networks exhibited excitatory intra-system connectivity and inhibitory inter-system connectivity. Patients were characterized by potentiated intra-system connections within the “emotional/sensory brain”, as well as over-inhibition of the “rational brain” by the “emotional/sensory brain”. The hierarchical architecture of the large-scale effective connectivity networks was then analyzed using a PageRank algorithm which revealed a shift of the controlling role of the “rational brain” to the “emotional/sensory brain” in the patients. These findings inform basic organization of distributed large-scale brain networks and furnish a better characterization of the neural mechanisms of depression, which may facilitate effective treatment.

Inter- and Intra- Hemispheric Interactions in Reading Ambiguous Words

The present study investigated how the brain processes words with multiple meanings. Specifically, we examined the inter- and intra-hemispheric connectivity of unambiguous words compared to two types of ambiguous words: homophonic homographs, which have multiple meanings mapped to a single phonological representation and orthography, and heterophonic homographs, which have multiple meanings mapped to different phonological representations but the same orthography. Using a semantic relatedness judgment task and effective connectivity analysis via Dynamic Causal Modeling (DCM) on previously published fMRI data (Bitan et al., 2017), we found that the two hemispheres compete in orthographic processing during the reading of unambiguous words. For heterophonic homographs, we observed increased connectivity within the left hemisphere, highlighting the importance of top-down re-activation of orthographic representations by phonological ones for considering alternative meanings. For homophonic homographs, we found a flow of information from the left to the right hemisphere and from the right to the left, indicating that the brain retrieves different meanings using different pathways. These findings provide novel insights into the complex mechanisms involved in language processing and shed light on the different communication patterns within and between hemispheres during the processing of ambiguous and unambiguous words.