Shijia Li

Effects of acute psychosocial stress on neural activity to emotional and neutral faces in a face recognition memory paradigm

Previous studies have shown that acute psychosocial stress impairs recognition of declarative memory and that emotional material is especially sensitive to this effect. Animal studies suggest a central role of the amygdala which modulates memory processes in hippocampus, prefrontal cortex and other brain areas. We used functional magnetic resonance imaging (fMRI) to investigate neural correlates of stress-induced modulation of emotional recognition memory in humans. Twenty-seven healthy, right-handed, non-smoker male volunteers performed an emotional face recognition task. During encoding, participants were presented with 50 fearful and 50 neutral faces. One hour later, they underwent either a stress (Trier Social Stress Test) or a control procedure outside the scanner which was followed immediately by the recognition session inside the scanner, where participants had to discriminate between 100 old and 50 new faces. Stress increased salivary cortisol, blood pressure and pulse, and decreased the mood of participants but did not impact recognition memory. BOLD data during recognition revealed a stress condition by emotion interaction in the left inferior frontal gyrus and right hippocampus which was due to a stress-induced increase of neural activity to fearful and a decrease to neutral faces. Functional connectivity analyses revealed a stress-induced increase in coupling between the right amygdala and the right fusiform gyrus, when processing fearful as compared to neutral faces. Our results provide evidence that acute psychosocial stress affects medial temporal and frontal brain areas differentially for neutral and emotional items, with a stress-induced privileged processing of emotional stimuli.

ADRA2B genotype differentially modulates stress-induced neural activity in the amygdala and hippocampus during emotional memory retrieval

RationaleNoradrenaline interacts with stress hormones in the amygdala and hippocampus to enhance emotional memory consolidation, but the noradrenergic-glucocorticoid interaction at retrieval, where stress impairs memory, is less understood.ObjectivesWe used a genetic neuroimaging approach to investigate whether a genetic variation of the noradrenergic system impacts stress-induced neural activity in amygdala and hippocampus during recognition of emotional memory.MethodsThis study is based on genotype-dependent reanalysis of data from our previous publication (Li et al. Brain Imaging Behav 2014). Twenty-two healthy male volunteers were genotyped for the ADRA2B gene encoding the α2B-adrenergic receptor. Ten deletion carriers and 12 noncarriers performed an emotional face recognition task, while their brain activity was measured with fMRI. During encoding, 50 fearful and 50 neutral faces were presented. One hour later, they underwent either an acute stress (Trier Social Stress Test) or a control procedure which was followed immediately by the retrieval session, where participants had to discriminate between 100 old and 50 new faces.ResultsA genotype-dependent modulation of neural activity at retrieval was found in the bilateral amygdala and right hippocampus. Deletion carriers showed decreased neural activity in the amygdala when recognizing emotional faces in control condition and increased amygdala activity under stress. Noncarriers showed no differences in emotional modulated amygdala activation under stress or control. Instead, stress-induced increases during recognition of emotional faces were present in the right hippocampus.ConclusionThe genotype-dependent effects of acute stress on neural activity in amygdala and hippocampus provide evidence for noradrenergic-glucocorticoid interaction in emotional memory retrieval.

Novelty seeking and reward dependence-related large-scale brain networks functional connectivity variation during salience expectancy: Variations During Salience Expectancy

A salience network (SN) anchored in the anterior insula (AI) and dorsal anterior cingulate cortex (dACC) plays a key role in switching between brain networks during salience detection and attention regulation. Previous fMRI studies have associated expectancy behaviors and SN activation with novelty seeking (NS) and reward dependence (RD) personality traits. To address the question of how functional connectivity (FC) in the SN is modulated by internal (expectancy‐related) salience assignment and different personality traits, 68 healthy participants performed a salience expectancy task using functional magnetic resonance imaging, and psychophysiological interaction analysis (PPI) was conducted to determine salience‐related connectivity changes during these anticipation periods. Correlation was then evaluated between PPI and personality traits, assessed using the temperament and character inventory of 32 male participants. During high salience expectancy, SN‐seed regions showed reduced FC to visual areas and parts of the default mode network, but increased FC to the central executive network. With increasing NS, participants showed significantly increasing disconnection between right AI and middle cingulate cortex when expecting high‐salience pictures as compared to low‐salience pictures, while increased RD also predicted decreased right dACC and caudate FC for high salience expectancy. Our findings suggest a direct link between personality traits and internal salience processing mediated by differential network integration of the SN. SN activity and coordination may therefore be moderated by novelty seeking and reward dependency personality traits, which are associated with risk of addiction. Hum Brain Mapp 38:4064–4077, 2017.

Altered task-specific deactivation in the default mode network depends on valence in patients with major depressive disorder

BACKGROUND Major depressive disorder (MDD) is a highly prevalent psychiatric condition in which patients often have difficulties regulating their emotions. Prior studies have shown that attention bias towards negative emotion is linked to activation in regions of the default mode network (DMN) in MDD individuals. Furthermore, MDD patients showed increased resting-state functional connectivity (FC) between the medial prefrontal cortex and other DMN structures. METHODS Twenty-one MDD patients that currently experiencing depressive episodes and twenty-five healthy control participants performed the current emotional expectancy paradigm in a gradient-echo SENSE-SPIRAL fMRI. Whole brain and psycho-physiological interaction (PPI) analysis were applied to explore the task-related brain activity and FCs. RESULTS Relative to healthy participants, we found MDD patients had greater activity in dorsal medial prefrontal cortex as a function of positive vs. neutral expectancy conditions. PPI results revealed a significant group difference of MDD patients having relatively decreased task-dependent decoupling from dorsal medial prefrontal cortex (DMPFC) towards posterior cingulate cortex (PCC) and parieto-occipital cortex during positive vs. neutral expectancy conditions, and patients exhibited a positive correlation between PPI (DMPFC and PCC) and anhedonia as measured via SHAPS during the same conditions. LIMITATIONS Modest sample size and lack of concurrent depressive episodes limit the generalizability of our findings. CONCLUSIONS In MDD patients, insufficient DMN decoupling might occur in response to positive expectancy conditions. Our findings are consistent with the hypothesis that high intrinsic DMN connectivity in MDD patients interfere with the down-regulation of intrinsic focus in order to incorporate information derived from external positive events.

The different effects of over-expressing murine NMDA receptor 2B subunit in the forebrain on conditioned taste aversion

The glutamate transmission system and the N-methyl-D-aspartate receptor (NMDA-R), in particular its 2B subunit (NR2B), have been reported to be possibly related to taste memory as a result of treatment with NMDA antagonists and agonists. In order to further study the role of the NR2B subunit in gustation memory, we applied four different taste aversive tasks to observe the behavior of a transgenic mice model in which the NR2B subunit was specifically over-expressed in the forebrain. We found that in both short- and long-term conditioned taste aversion (CTA) experiments, mice with forebrain expression of the NR2B transgene (Tg) showed significantly enhanced CTA 2 days after training. However, both the Tg and the wild-type (Wt) mice shared the same level of aversive memory on the 30th day after training. In both fast and slow extinction experiments, Tg mice maintained a higher CTA memory than that of control mice in most extinction trials. The third experiment, which involved testing the memory for familiar taste, demonstrated that NR2B augmentation had no benefit on the latent inhibition (LI) of CTA. In addition, the last experiment (two-taste LI) showed a suppression of enhanced CTA in Tg mice when the mice were exposed to both novel and familiar tastes. These data suggested that forebrain NR2B over-expression had different effects on gustatory learning and memory. The transgenic animals were only sensitive to novel but not familiar tastes, and up-regulation of NR2B resulted in enhanced CTA function for only a short period of time.

Factors Influencing the Cardiovascular Response to Subanesthetic Ketamine: A Randomized, Placebo-Controlled Trial

Abstract Background The increasing use of ketamine as a potential rapid-onset antidepressant necessitates a better understanding of its effects on blood pressure and heart rate, well-known side effects at higher doses. For the subanesthetic dose used for depression, potential predictors of these cardiovascular effects are important factors influencing clinical decisions. Since ketamine influences the sympathetic nervous system, we investigated the impact of autonomic nervous system-related factors on the cardiovascular response: a genetic polymorphism in the norepinephrine transporter and gender effects. Methods Blood pressure and heart rate were monitored during and following administration of a subanesthetic dose of ketamine or placebo in 68 healthy participants (mean age 26.04 ±5.562 years) in a double-blind, randomized, controlled, parallel-design trial. The influences of baseline blood pressure/heart rate, gender, and of a polymorphism in the norepinephrine transporter gene (NET SLC6A2, rs28386840 [A-3081T]) on blood pressure and heart rate changes were investigated. To quantify changes in blood pressure and heart rate, we calculated the maximum change from baseline (ΔMAX) and the time until maximum change (TΔMAX). Results Systolic and diastolic blood pressure as well as heart rate increased significantly upon ketamine administration, but without reaching hypertensive levels. During administration, the systolic blood pressure at baseline (TP0Sys) correlated negatively with the time to achieve maximal systolic blood pressure (TΔMAXSys, P<.001). Furthermore, women showed higher maximal diastolic blood pressure change (ΔMAXDia, P<.001) and reached this peak earlier than men (TΔMAXDia, P=.017) at administration. NET rs28386840 [T] carriers reached their maximal systolic blood pressure during ketamine administration significantly earlier than [A] homozygous (TΔMAXSys, P=.030). In a combined regression model, both genetic polymorphism and TP0Sys were significant predictors of TΔMAXSys (P<.0005). Conclusions Subanesthetic ketamine increased both blood pressure and heart rate without causing hypertensive events. Furthermore, we identified gender and NET rs28386840 genotype as factors that predict increased cardiovascular sequelae of ketamine administration in our young, healthy study population providing a potential basis for establishing monitoring guidelines.

Does Growing up in Urban Compared to Rural Areas Shape Primary Emotional Traits

Growing up in urban areas represents a possible risk factor in the genesis of psychopathologies. The aim of the present study was to investigate the link between urbanicity variables and indicators for psychiatric disorders. We investigated a potential association between primary emotional traits and urbanicity variables in 324 individuals from Germany and 713 individuals from China. Higher scores in the urbanicity index in childhood were inversely associated with FEAR and SADNESS only in adult Chinese females. These effects seemed to be driven by living in Chinese mega-cities, because a parallel sample from Germany and China (contrasting upbringing in cities with the categories <10,000 inhabitants, ≥10,000 inhabitants (but <100,000), and ≥100,000 inhabitants) resulted in weaker, but more similar effects in females in both countries. Additional associations could be observed with higher PLAY and urban upbringing in Chinese males. The results seem surprising, given an expectation of adverse emotional effects from growing up in todays’ mega-cities compared to rural areas. Although we do not want to over-interpret our findings (given rather small correlations and multiple testing issues), they should encourage researchers to consider including urbanicity variables in personality neuroscience and personality oriented clinical psychiatric research.

Motivation but not valence modulates neuroticism-dependent cingulate cortex and insula activity

Neuroticism has been found to specifically modulate amygdala activations during differential processing of valence and motivation while other brain networks yet are unexplored for associated effects. The main purpose of this study was to investigate whether neural mechanisms processing valence or motivation are prone to neuroticism in the salience network (SN), a network that is anchored in the anterior cingulate cortex (ACC) and the anterior insula. This study used functional magnetic resonance imaging (fMRI) and an approach/avoid emotional pictures task to investigate brain activations modulated by pictures’ valence or motivational status between high and low neurotic individuals. We found that neuroticism‐dependent SN and the parahippocampal‐fusiform area activations were modulated by motivation but not valence. Valence in contrast interacted with neuroticism in the lateral orbitofrontal cortex. We suggested that neuroticism modulated valence and motivation processing, however, under the influence of the two distinct networks. Neuroticism modulated the motivation through the SN while it modulated the valence through the orbitofrontal networks.

Neurobiological Augmentation of Psychotherapy in Treatment Resistant Depression

A substantial number of patients diagnosed with major depression disorder have poor or no response to standard antidepressive drugs. Recent studies showed that ketamine promotes a rapid and sustained antidepressive effect and also promotes neuroplasticity in the regions involved in MDD psychopathology. In this review we summarize the molecular mechanisms of ketamine action, behavioral changes upon administration and the psychotherapeutic implication of ketamine-induced modification of learning and memory processes. Then, from a multi-point perspective, we argue for possible long-term benefits of NMDA receptor modulation on psychotherapy in patients with major depressive disorder. We embed this proposed augmentation strategy into existing literature on the role of NMDA-receptor mediating learning and conclude on recent psychotherapeutic implications for the use of ketamine within multidimensional treatment consideration.