Biology subjects

Fu, M.

Publications and source records attributed to Fu, M..

43 records · Page 3Linked to original sources

bioRxiv2019

Inter-subject phase synchronization differentiates neural networks underlying physical pain empathy

Recent approaches for understanding the neural basis of pain empathy emphasize the dynamic construction of neural networks underlying this multifaceted social cognitive process. Inter-subject phase synchronization (ISPS) is an approach for exploratory analysis of task-based fMRI data that reveals brain networks dynamically synchronized to task-features across participants. We applied ISPS to task-fMRI data assessing vicarious pain empathy in a large sample of healthy participants (n=238). The task employed physical (limb) and affective (faces) painful and corresponding non-painful visual stimuli. ISPS revealed two distinct networks synchronized during physical pain observation, one encompassing anterior insula and midcingulate regions strongly engaged in (vicarious) pain, and another encompassing parietal and inferior frontal regions associated with social cognitive processes which may further modulate and support the physical pain empathic response. No robust network synchronization was observed while processing affective pain, possibly reflecting high inter-individual variation in response to socially transmitted pain experiences. ISPS also revealed networks related to task onset or general processing of physical (limb) or affective (face) stimuli which encompassed networks engaged in object manipulation or face processing, respectively. Together, the ISPS approach permits segregation of networks engaged in different psychological processes, providing additional insight into shared neural mechanisms of empathy for physical pain, but not affective pain, across individuals.

neuroscience↗

bioRxiv2019

Cytosolic Ca2+ modulates Golgi structure through PKC-mediated GRASP55 phosphorylation

It has been well documented that the endoplasmic reticulum (ER) responds to cellular stresses through the unfolded protein response (UPR), but it is unknown how the Golgi responds to similar stresses. In this study, we treated HeLa cells with ER stress inducers, thapsigargin (TG), tunicamycin (Tu) and Dithiothreitol (DTT), and found that only TG treatment caused Golgi fragmentation. TG induced Golgi fragmentation at a low dose and short time when UPR was undetectable, demonstrating that Golgi fragmentation occurs independently of ER stress. Further experiments demonstrated that TG induces Golgi fragmentation through elevated intracellular Ca2+ and protein kinase C (PKC) activity, which phosphorylates the Golgi stacking protein GRASP55. Significantly, activation of PKC with other activating or inflammatory agents, including Phorbol 12-myristate 13-acetate (PMA) and histamine, modulates the Golgi structure in a similar fashion. Hence, our study revealed a novel mechanism through which increased cytosolic Ca2+ modulates Golgi structure and function.

cell biology↗

bioRxiv2019

Gene - Environment Interaction: A TPH2 polymorphism and early life stress shape brain architecture and anxious avoidant behavior

BackgroundEarly life stress has been associated with emotional dysregulations and altered architecture of limbic-prefrontal brain systems engaged in emotional processing. Serotonin regulates both, developmental and experience-dependent neuroplasticity in these circuits. Central serotonergic biosynthesis rates are regulated by Tryptophan hydroxylase 2 (TPH2), and transgenic animal models suggest that TPH2-gene associated differences in serotonergic signaling mediate the impact of aversive early life experiences on a phenotype characterized by anxious avoidance. MethodsThe present study employed an imaging genetics approach that capitalized on individual differences in a TPH2 polymorphism (703G/T; rs4570625) to determine whether differences in serotonergic signaling modulate the effects of early life stress on brain structure and function and punishment sensitivity in humans (n = 252). ResultsHigher maltreatment exposure before the age of 16 was associated with increased gray matter volumes in a circuitry spanning thalamic-limbic-prefrontal regions and decreased intrinsic communication in limbic-prefrontal circuits selectively in TT carriers. In an independent replication sample, associations between higher early life stress and increased frontal volumes in TT carriers were confirmed. On the phenotype level, the genotype moderated the association between higher early life stress exposure and higher punishment sensitivity. In TT carriers, the association between higher early life stress exposure and punishment sensitivity was critically mediated by increased thalamic-limbic-prefrontal volumes. ConclusionsThe present findings suggest that early life stress shapes the neural organization of the limbic-prefrontal circuits in interaction with individual variations in the TPH2 gene to promote a phenotype characterized by facilitated threat avoidance, thus promoting early adaptation to an adverse environment.

neuroscience↗

bioRxiv2019

Comparison of three different eye-tracking tasks for distinguishing autistic from typically developing children and autistic symptom severity

Altered patterns of visual social attention preference detected using eye-tracking and a variety of different paradigms are increasingly proposed as sensitive biomarkers for autism spectrum disorder. However, few eye tracking studies have compared the relative efficacy of different paradigms to discriminate between autistic compared with typically developing children and their sensitivity to specific symptoms. To target this issue, the current study used three common eye tracking protocols contrasting social versus non-social stimuli in young (2-7 years old) Chinese autistic (n = 35) and typically developing (n = 34) children matched for age and gender. Protocols included dancing people vs. dynamic geometrical images, biological motion (dynamic light point walking human or cat) vs. non-biological motion (scrambled controls) and child playing with toy vs. toy alone. Although all three paradigms differentiated autistic and typically developing children, the dancing people versus dynamic geometry pattern paradigm was the most effective, with autistic children showing marked reductions in visual preference for dancing people and correspondingly increased one for geometric patterns. Furthermore, this altered visual preference in autistic children was correlated with the ADOS social affect score and had the highest discrimination accuracy. Our results therefore indicate that decreased visual preference for dynamic social stimuli may be the most effective visual attention-based paradigm for use as a biomarker for autism in Chinese children. Clinical trial ID: NCT03286621 (clinicaltrials.gov); Clinical trial name: Development of Eye-tracking Based Markers for Autism in Young Children. Lay summaryEye-tracking measures may be useful in aiding diagnosis and treatment of autism, although it is unclear which specific tasks are optimal. Here we compare the ability of three different social eye-gaze tasks to discriminate between autistic and typically developing young Chinese children and their sensitivity to specific autistic symptoms. Our results show that a dynamic task comparing visual preference for social (individuals dancing) versus geometric patterns is the most effective both for diagnosing autism and sensitivity to its social affect symptoms.

clinical trials↗

bioRxiv2018

Common and dissociable contributions of alexithymia and autism to domain-specific interoceptive dysregulations - a dimensional neuroimaging approach

Alexithymia represents a transdiagnostic marker across psychiatric entities associated with emotional impairments, including autism spectrum disorders (ASD). Accumulating evidence suggests that interoceptive dysfunctions that underpin the core symptomatic emotion recognition and empathy deficits in ASD may be contributed to by high levels of alexithymia rather than autistic symptoms per se. However, previous findings are hampered by generally elevated alexithymia in ASD patients, and thus were not able to differentiate common and distinct contributions across the entire spectrum of variations of autism and alexithymia. Moreover, the multi-factorial nature of the domains affected, such as distinct neural reactivity towards perceiving physical and affective pain, has not been accounted for. Against this background the present fMRI study employed a dimensional trait approach in n = 242 healthy subjects to determine common and distinct associations between both traits and pain empathic responses towards physical and affective pain. Higher levels of alexithymia associated with increased left anterior insula pain empathic reactivity. Disentangling these effects revealed a positive association during perceived physical pain, but a negative one during affective pain. No significant associations with trait autism were found, but an interaction effect between the trait dimensions was observed in the mid-cingulate cortex. Moderation analysis demonstrated that trait autism only impacted mid-cingulate reactivity towards physical pain in high alexithymia subjects, whereas reactivity towards affective pain was specifically associated with trait autism in low alexithymia subjects. Findings confirm previous patient studies suggesting that alexithymia rather than autism per se may drive altered insula pain empathic reactivity. Importantly, the present approach allowed for the first time to demonstrate that the impact of alexithymia on insula reactivity varies as a function of the pain empathic domain and that effects on other core empathy nodes evolve in interaction with trait autism.

neuroscience↗

bioRxiv2018

Impaired cognitive performance under psycho-social stress in cannabis dependence is mediated by attenuated precuneus activity

BackgroundDeficient regulation of stress plays an important role in the escalation of substance use, addiction and relapse. Accumulating evidence suggests dysregulations in cognitive and reward-related processes and the underlying neural circuitry in cannabis dependence. However, despite the important regulatory role of the endocannabinoid system in the stress response, associations between chronic cannabis use and altered stress processing on the neural level have not been systematically examined. MethodsAgainst this background, the present functional magnetic resonance imaging (fMRI)study examined psycho-social stress processing in cannabis-dependent males (n = 28) and matched controls (n = 23) using an established stress-induction paradigm (Montreal Imaging Stress Task) that combines computerized (adaptive) mental arithmetic challenges with social evaluative threat. ResultsDuring psycho-social stress exposure, but not the no-stress condition, cannabis users demonstrated impaired performance relative to controls. In contrast, levels of experienced stress and cardiovascular stress responsivity did not differ from controls. Functional MRI data revealed that stress-induced performance deteriorations in cannabis users were accompanied by decreased precuneus activity and increased connectivity of this region with the dorsal medial prefrontal cortex. LimitationsOnly male cannabis-dependent users were examined, the generalizability in female users remains to be determined. ConclusionTogether, the present findings provide first evidence for exaggerated stress-induced cognitive performance deteriorations in cannabis users. The neural data suggest that deficient stress-related dynamics of the precuneus may mediate the deterioration of performance on the behavioral level.

neuroscience↗

bioRxiv2017

IFNα, a potential biomarker for stress vitiligo risk

Neural hypothesis has become an important aspect of vitiligo, yet without corresponding diagnostic indicators. We preliminarily found 32 cases of vitiligo patients with certain aggregation of mental factors. In peripheral blood mononuclear cells (PBMCs) of these patients, transcriptome analyses revealed that the circulation expression of a type I interferon (IFN-I)-dependent genes was induced. Also, serum IFN was elevated in vitiligo patients with depression. Therefore, our hypothesis is whether IFN levels predict the occurrence of psychiatric vitiligo. Through the establishment of stress-induced depigmentation model, serum IFN also showed increase. Intracerebroventricular and subcutaneous IFN injection can both elicit not only depressive behavior but also vitiligo-like characteristics. Mechanistically, central IFN induces the release of dorsal root ganglion (DRG) substance P (SP) to inhibit melanogenesis. Peripheral IFN disturbs cutaneous-neuro-endocrine microenvironment. Type I IFN (IFN) pathway-related genes in stress vitiligo were significantly discriminating from non-stress vitiligo, while that of type II IFN pathway was not.

physiology↗