Neurobiological Underpinnings of Hyperarousal in Depression: A Comprehensive Review.

Patients with major depressive disorder (MDD) exhibit an abnormal physiological arousal pattern known as hyperarousal, which may contribute to their depressive symptoms. However, the neurobiological mechanisms linking this abnormal arousal to depressive symptoms are not yet fully understood. In this review, we summarize the physiological and neural features of arousal, and review the literature indicating abnormal arousal in depressed patients. Evidence suggests that a hyperarousal state in depression is characterized by abnormalities in sleep behavior, physiological (e.g., heart rate, skin conductance, pupil diameter) and electroencephalography (EEG) features, and altered activity in subcortical (e.g., hypothalamus and locus coeruleus) and cortical regions. While recent studies highlight the importance of subcortical-cortical interactions in arousal, few have explored the relationship between subcortical-cortical interactions and hyperarousal in depressed patients. This gap limits our understanding of the neural mechanism through which hyperarousal affects depressive symptoms, which involves various cognitive processes and the cerebral cortex. Based on the current literature, we propose that the hyperconnectivity in the thalamocortical circuit may contribute to both the hyperarousal pattern and depressive symptoms. Future research should investigate the relationship between thalamocortical connections and abnormal arousal in depression, and explore its implications for non-invasive treatments for depression.

Specificity in the processing of a subject's own name.

Subject's own name (SON) is widely used in both daily life and the clinic. Event-related potential (ERP)-based studies have previously detected several ERP components related to SON processing; however, as most of these studies used SON as a deviant stimulus, it was not possible to determine whether these components were SON-specific. To identify SON-specific ERP components, we adopted a passive listening task with EEG data recording involving 25 subjects. The auditory stimuli were a SON, a friend's name (FN), an unfamiliar name (UN) selected from other subjects' names and seven different unfamiliar names (DUNs). The experimental settings included Equal-probabilistic, Frequent-SON, Frequent-FN and Frequent-UN conditions. The results showed that SON consistently evoked a frontocentral SON-related negativity (SRN) within 210-350 ms under all conditions, which was not detected with the other names. Meanwhile, a late positive potential evoked by SON was found to be affected by stimulus probability, showing no significant difference between the SON and the other names in the Frequent-SON condition, or between the SON and a FN in the Frequent-UN condition. Taken together, our findings indicated that the SRN was a SON-specific ERP component, suggesting that distinct neural mechanism underly the processing of a SON.

Brain State Relays Self-Processing and Heartbeat-Evoked Cortical Responses.

The self has been proposed to be grounded in interoceptive processing, with heartbeat-evoked cortical activity as a neurophysiological marker of this processing. However, inconsistent findings have been reported on the relationship between heartbeat-evoked cortical responses and self-processing (including exteroceptive- and mental-self-processing). In this review, we examine previous research on the association between self-processing and heartbeat-evoked cortical responses and highlight the divergent temporal-spatial characteristics and brain regions involved. We propose that the brain state relays the interaction between self-processing and heartbeat-evoked cortical responses and thus accounts for the inconsistency. The brain state, spontaneous brain activity which highly and continuously changes in a nonrandom way, serves as the foundation upon which the brain functions and was proposed as a point in an extremely high-dimensional space. To elucidate our assumption, we provide reviews on the interactions between dimensions of brain state with both self-processing and heartbeat-evoked cortical responses. These interactions suggest the relay of self-processing and heartbeat-evoked cortical responses by brain state. Finally, we discuss possible approaches to investigate whether and how the brain state impacts the self-heart interaction.

Identifying patients with cognitive motor dissociation using resting-state temporal stability.

Using task-dependent neuroimaging techniques, recent studies discovered a fraction of patients with disorders of consciousness (DOC) who had no command-following behaviors but showed a clear sign of awareness as healthy controls, which was defined as cognitive motor dissociation (CMD). However, existing task-dependent approaches might fail when CMD patients have cognitive function (e.g., attention, memory) impairments, in which patients with covert awareness cannot perform a specific task accurately and are thus wrongly considered unconscious, which leads to false-negative findings. Recent studies have suggested that sustaining a stable functional organization over time, i.e., high temporal stability, is crucial for supporting consciousness. Thus, temporal stability could be a powerful tool to detect the patient's cognitive functions (e.g., consciousness), while its alteration in the DOC and its capacity for identifying CMD were unclear. The resting-state fMRI (rs-fMRI) study included 119 participants from three independent research sites. A sliding-window approach was used to investigate global and regional temporal stability, which measured how stable the brain's functional architecture was across time. The temporal stability was compared in the first dataset (36/16 DOC/controls), and then a Support Vector Machine (SVM) classifier was built to discriminate DOC from controls. Furthermore, the generalizability of the SVM classifier was tested in the second independent dataset (35/21 DOC/controls). Finally, the SVM classifier was applied to the third independent dataset, where patients underwent rs-fMRI and brain-computer interface assessment (4/7 CMD/potential non-CMD), to test its performance in identifying CMD. Our results showed that global and regional temporal stability was impaired in DOC patients, especially in regions of the cingulo-opercular task control network, default-mode network, fronto-parietal task control network, and salience network. Using temporal stability as the feature, the SVM model not only showed good performance in the first dataset (accuracy = 90%), but also good generalizability in the second dataset (accuracy = 84%). Most importantly, the SVM model generalized well in identifying CMD in the third dataset (accuracy = 91%). Our preliminary findings suggested that temporal stability could be a potential tool to assist in diagnosing CMD. Furthermore, the temporal stability investigated in this study also contributed to a deeper understanding of the neural mechanism of consciousness.

Dual interaction between heartbeat-evoked responses and stimuli.

Heartbeat-evoked responses (HERs) can interact with external stimuli and play a crucial role in shaping perception, self-related processes, and emotional processes. On the one hand, the external stimulus could modulate HERs. On the other hand, the HERs could affect cognitive processing of the external stimulus. Whether the same neural mechanism underlies these two processes, however, remains unclear. Here, we investigated this interactive mechanism by measuring HERs using magnetoencephalography (MEG) and two name perception tasks. Specifically, we tested (1) how hearing a subject's own name (SON) modulates HERs and (2) how the judgment of an SON is biased by prestimulus HERs. The results showed a dual interaction between HERs and SON. In particular, SON can modulate HERs for heartbeats occurring from 200 to 1200 ms after SON presentation. In addition, prestimulus HERs can bias the SON judgment when a stimulus is presented. Importantly, MEG activities from these two types of interactions differed in spatial and temporal patterns, suggesting that they may be associated with distinct neural pathways. These findings extend our understanding of brain-heart interactions.

Decoding subject's own name in the primary auditory cortex.

Current studies have shown that perception of subject's own name (SON) involves multiple multimodal brain regions, while activities in unimodal sensory regions (i.e., primary auditory cortex) and their interaction with multimodal regions during the self-processing remain unclear. To answer this, we combined multivariate pattern analysis and dynamic causal modelling analysis to explore the regional activation pattern and inter-region effective connection during the perception of SON. We found that SON and other names could be decoded from the activation pattern in the primary auditory cortex. In addition, we found an excitatory effect of SON on connections from the anterior insula/inferior frontal gyrus to the primary auditory cortex, and to the temporoparietal junction. Our findings extended the current knowledge of self-processing by showing that primary auditory cortex could discriminate SON from other names. Furthermore, our findings highlighted the importance of influence of the insula on the primary auditory cortex during self-processing.

Distinct Effects of Stimulus Repetition on Various Temporal Stages of Subject's Own Name Processing.

The self is one of the most important concepts in psychology, which is of great significance for human survival and development. As an important self-related stimulus, the subject's own name (SON) shows great advantages in cognitive and social processing and is widely used as an oddball stimulus in previous studies. However, it remained unknown whether the multiple repetition of stimulus would have similar influence on the neural response to SON and the other names under equal probability. In this study, adopting EEG and an equal-probability paradigm, we first detected the SON-related ERP components which could differentiate SON from other names, and then investigated how these components are influenced by repeated exposure of the stimulus. Our results showed that SON evoked an earlier SON-related negativity (SRN) at the fronto-central region and a late positive potential (LPP) at the centro-parietal region. More intriguingly, the earlier SRN demonstrated reduction after multiple repetitions, whereas LPP did not exhibit significant changes. In conclusion, these findings revealed that multiple repetitions of the stimulus might influence the various temporal stages in SON-related processing and highlighted the robustness of the late stage in this processing.