Family Conflict Associated With Intrinsic Hippocampal-OFC Connectivity in Adolescent Depressive Disorder

BackgroundFamily environment and life events have long been suggested to be associated with adolescent depression. The hippocampus plays a crucial role in the neural mechanism of major depressive disorder (MDD) through memory during stressful events. However, few studies have explored the exact neural mechanisms underlying these associations. Thus, the current study aimed to explore alterations in hippocampal functional connectivity (FC) in adolescent MDD based on resting-state functional magnetic resonance imaging and further investigate the relationship between hippocampal FC, environmental factors, and clinical symptom severity.MethodsHippocampal FC was calculated using the seed-based approach with the bilateral hippocampus as the seed for 111 adolescents with and without MDD; comparisons were made between participants with MDD and controls. We applied the Chinese version of the Family Environment Scale (FES-CV) and Adolescents Self-Rating Life Events Checklist (ASLEC) to evaluate family environment and life stress. Their relationship with hippocampal FC alterations was also investigated.ResultsWe found that compared to controls, adolescents with MDD showed decreased connectivity between the left hippocampus and bilateral orbital frontal cortex (OFC) and right inferior temporal gyrus. In addition, the hippocampal-OFC connectivity was negatively correlated with conflict scores of the FES-CV in the MDD group and mediated the association between family conflict and depressive and anxiety symptoms.ConclusionOur findings are novel in the field and demonstrate how family conflict contributes to MDD symptomatology through hippocampal-OFC connectivity; these findings may provide potential targets for personalized treatment strategies.

Neuromuscular Stimulation as an Intervention Tool for Recovery from Upper Limb Paresis after Stroke and the Neural Basis

Neuromodulators at the periphery, such as neuromuscular electrical stimulation (NMES), have been developed as add-on tools to regain upper extremity (UE) paresis after stroke, but this recovery has often been limited. To overcome these limits, novel strategies to enhance neural reorganization and functional recovery are needed. This review aims to discuss possible strategies for enhancing the benefits of NMES. To date, NMES studies have involved some therapeutic concerns that have been addressed under various conditions, such as the time of post-stroke and stroke severity and/or with heterogeneous stimulation parameters, such as target muscles, doses or durations of treatment and outcome measures. We began by identifying factors sensitive to NMES benefits among heterogeneous conditions and parameters, based on the “progress rate (PR)”, defined as the gains in UE function scores per intervention duration. Our analysis disclosed that the benefits might be affected by the target muscles, stroke severity and time period after stroke. Likewise, repetitive peripheral neuromuscular magnetic stimulation (rPMS) is expected to facilitate motor recovery, as already demonstrated by a successful study. In parallel, our efforts should be devoted to further understanding the precise neural mechanism of how neuromodulators make UE function recovery occur, thereby leading to overcoming the limits. In this study, we discuss the possible neural mechanisms.

Parent-Child Dyads with Greater Parenting Stress Exhibit Enhanced Inter-Brain Synchrony During Shared Play

Parent-child dyads who are mutually attuned to each other during social interactions display interpersonal synchrony that can be observed overtly, in the form of joint behaviours, and biologically, such as through the temporal coordination of brain signals called inter-brain synchrony. Joint play provides ample opportunities for parent-child dyads to engage in matching interactions which not just facilitate the formation of bonds but also alleviate parenting stress in caregivers. Despite the beneficial effects of play on parents and the parent-child relationship, no study has investigated the dyadic neural mechanism by which this occurs. The present functional Near-infrared Spectroscopy (fNIRS) study aimed to examine the association between parenting stress and inter-brain synchrony in the prefrontal cortex of 31 mother-child and 29 father-child dyads while they engaged in shared play for 10 minutes. Shared play was miro-analytically coded into joint (i.e., in-phase matching of dyadic behaviours) and non-joint (i.e., no matching of dyadic behaviours) segments. Inter-brain synchrony was computed using cross-correlations over 15 s, 20 s, 25 s, 30 s and 35 s fixed-length windows of joint and non-joint play segments. Analyses of Covariance revealed that dyads with more parenting stress exhibited greater inter-brain synchrony in the frontal left cluster of the prefrontal cortex, but only for the 35 s fixed-length window. This finding suggests that continuous and positive instances of joint play may disproportionately benefit dyads who reported greater parenting stress, entraining underlying brain activation patterns involved in social cognition. Mother-child dyads also showed greater inter-brain synchrony than father-child dyads, alluding to possible gender differences in the effect of play on dyads. Findings present evidence of a potential dyadic neural pathway by which play benefits the parent-child relationship.

Altered Topological Organization of Functional Brain Networks in Betel Quid Dependence: A Resting-State Functional MRI Study

Background: Betel quid dependence (BQD) is associated with abnormalities in the widespread inter-regional functional connectivity of the brain. However, no studies focused on the abnormalities in the topological organization of brain functional networks in chewers in Mainland China.Methods: In the current study, resting-state functional magnetic resonance images were acquired from 53 BQD individuals and 37 gender- and age-matched healthy controls (HCs). A functional network was constructed by calculating the Pearson correlation coefficients among 90 subregions in the human Brainnetome Atlas. The topological parameters were compared between BQD individuals and HCs.Results: The results showed that BQD individuals presented a small-world topology, but the normalized characteristic path length (λ) increased compared with HCs (0.563 ± 0.030 vs. 0.550 ± 0.027). Compared to HCs, BQ chewers showed increased betweenness centrality (Be) in the right supplementary motor area, right medial superior frontal gyrus, right paracentral lobule, right insula, left posterior cingulate gyrus, right hippocampus, right post-central gyrus, right superior parietal gyrus, and right supramarginal gyrus, while decreased Be was found in the orbitofrontal area and temporal area, which is associated with reward network, cognitive system, and default mode network. The area under the curve (AUC) value of λ displayed a positive correlation with the duration of BQ chewing (r = 0.410, p = 0.002).Conclusions: The present study revealed the disruption of functional connectome in brain areas of BQD individuals. The findings may improve our understanding of the neural mechanism of BQD from a brain functional network topological organization perspective.

Effective connectivity of LSD-induced ego dissolution

Classic psychedelic-induced ego dissolution involves a shift in the sense of self and blurring of boundary between the self and the world. A similar phenomenon is identified in psychopathology and is associated to the balance of anticorrelated activity between the default mode network (DMN) – which directs attention inwards – and the salience network (SN) – which recruits the dorsal attention network (DAN) to direct attention outward. To test whether change in anticorrelated networks underlie the peak effects of LSD, we applied dynamic causal modeling to infer effective connectivity of resting state functional MRI scans from a study of 25 healthy adults who were administered 100mg of LSD, or placebo. We found that change in inhibitory effective connectivity from the SN to DMN became excitatory, and inhibitory effective connectivity from DMN to DAN decreased under the peak effect of LSD. These changes in connectivity reflect diminution of the anticorrelation between resting state networks that may be a key neural mechanism of LSD-induced ego dissolution. Our findings suggest the hierarchically organised balance of resting state networks is a central feature in the construct of self.SignificanceThe findings can inform the parallel between the maintenance of subject-object boundary and changes to anticorrelated canonical resting state brain networks. Effective connectivity informs the hierarchical organisation of brain networks underlying modes of perception. Moreover, the anticorrelation of brain networks is an important measure of mental function. Understanding the neural mechanisms of anticorrelation change under psychedelics help identify its relationship to psychosis and its association to psychedelic assisted therapeutic outcomes.

Combined In Silico, Ex Vivo, and In Vivo Assessment of L-17, a Thiadiazine Derivative with Putative Neuro- and Cardioprotective and Antidepressant Effects

Depression associated with poor general medical condition, such as post-stroke (PSD) or post-myocardial infarction (PMID) depression, is characterized by resistance to classical antidepressants. Special treatment strategies should thus be developed for these conditions. Our study aims to investigate the mechanism of action of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17), a recently designed thiadiazine derivative with putative neuro- and cardioprotective and antidepressant-like effects, using combined in silico (for prediction of the molecular binding mechanisms), ex vivo (for assessment of the neural excitability using c-Fos immunocytochemistry), and in vivo (for direct examination of the neuronal excitability) methodological approaches. We found that the predicted binding affinities of L-17 to serotonin (5-HT) transporter (SERT) and 5-HT3 and 5-HT1A receptors are compatible with selective 5-HT serotonin reuptake inhibitors (SSRIs) and antagonists of 5-HT3 and 5-HT1A receptors, respectively. L-17 robustly increased c-Fos immunoreactivity in the amygdala and decreased it in the hippocampus. L-17 dose-dependently inhibited 5-HT neurons of the dorsal raphe nucleus; this inhibition was partially reversed by the 5-HT1A antagonist WAY100135. We suggest that L-17 is a potent 5-HT reuptake inhibitor and partial antagonist of 5-HT3 and 5-HT1A receptors; the effects of L-17 on amygdaloid and hippocampal excitability might be mediated via 5-HT, and putatively mediate the antidepressant-like effects of this drug. Since L-17 also possesses neuro- and cardioprotective properties, it can be beneficial in PSD and PMID. Combined in silico predictions with ex vivo neurochemical and in vivo electrophysiological assessments might be a useful strategy for early assessment of the efficacy and neural mechanism of action of novel CNS drugs.

Neural mechanism of experience-dependent sensory gain control in C. elegans

Animals' sensory systems adjust their responsiveness to environmental stimuli that vary greatly in their intensity. Here we report the neural mechanism of experience-dependent sensory adjustment, especially gain control, in the ASH nociceptive neurons in Caenorhabditis elegans. Using calcium imaging under gradual changes in stimulus intensity, we find that the ASH neurons of naive animals respond to concentration increases in a repulsive odor 2-nonanone regardless of the magnitude of the concentration increase. However, after preexposure to the odor, the ASH neurons exhibit significantly weak responses to a small gradual increase in odor concentration while their responses to a large gradual increase remain strong. Thus, preexposure changes the slope of stimulus-response relationships (i.e., gain control). Behavioral analysis suggests that this gain control contributes to the preexposure-dependent enhancement of odor avoidance behavior. Mathematical analysis reveals that the ASH response consists of fast and slow components, and that the fast component is specifically suppressed by preexposure. In addition, genetic analysis suggests that G protein signaling is required for the fast component. Thus, our integrative study demonstrates how prior experience dynamically modulates stimulus-response relationships in sensory neurons, eventually leading to adaptive modulation of behavior.

The Association between Economic Inequality and Adolescents' Prosocial Behavior: Evidence from Brain Potentials and Genes

The inherent neural mechanism in prosocial behavior and its developmental trajectory are inadequately understood. To address the above gaps, a two-pronged empirical approach, such as experimental approach (e.g., evidence from event-related potentials) and longitudinal questionnaire approach (e.g., latent growth model), is urgently needed to depict a more complete picture of this phenomenon. While both the experimental approach and the correlational approach have their strengths and limitations, they complement one another. In study 1, I sought to replicate prior research and reexamine the relation between SES and adolescents' prosocial behaviors in the ERPs experiment. In study 2, I intend to establish empirical support for the interaction between economic inequality and SES on adolescents' prosocial behavior and the underlying neural mechanism. In these studies, I manipulate the economic inequality and SES in the laboratory experiment to draw causal inferences. Considering the limited external validity of the experiment, study 3 aims to provide longitudinal support for the processing mechanism that explains how economic inequality and SES affect the developmental trajectory of adolescents' prosocial behavior.

Alteration of Behavioral Inhibitory Control in High-Altitude Immigrants

Behavioral inhibitory control (BIC) acts as a key cognitive ability, which is essential for humans to withhold inappropriate behaviors. Meanwhile, many studies reported that long-term exposure to high altitude (HA) may affect cognitive ability. However, it is not clear whether long-term exposure to HAs may affect the BIC of an individual. To clarify the role of altitude in the behavioral control of adults and the underlying neural mechanism, we explored the BIC neural activity profiles of healthy immigrants from low-altitude (LA) regions to HA regions. Combining a two-choice oddball paradigm and electrophysiological techniques, this study monitored the N2 and P3 event-related components and neural oscillations across LA and HA groups. Results showed longer reaction times (RTs) for the HA group than the LA group. Relative to the LA group, lower N2 and P3 amplitudes were observed for the HA group. Significant positive correlations were also found between P3 amplitude and theta/delta band power across both groups. Importantly, lower theta/delta band powers were only observed for the HA group under the deviant condition. Collectively, these findings suggest that long-term exposure to HAs may attenuate BIC during the response inhibition stage and provide valuable insights into the neurocognitive implications of environmental altitude on BIC.