Offline beats online: transcranial direct current stimulation timing influences on working memory The n-back task is an established measure of an individual’s working memory. In this task, participants have to continuously update their working memory to react to a stimulus correctly. For the verbal n-back task in particular, the left dorsolateral prefrontal cortex (lDLPFC) plays a key role in working memory updating and a higher activation of the lDLPFC has been linked to an increase in performance. Transcranial direct current stimulation (tDCS) has been used extensively to investigate its effect on working memory but it remains unclear whether online or offline tDCS produces the largest modulation of task performance. To tackle this question, we used anodal tDCS to stimulate the lDLPFC in a repeated measures design and compared offline, online and sham stimulation. A 9 cm2 anode was always placed over the lDLPFC while the 35 cm2 cathode was positioned over the left deltoid. In a sample of N = 63 healthy adults, we found a significantly larger performance improvement, in correct reaction times as well as accuracy rates, after offline tDCS compared to online or sham stimulation. This pattern of results provides evidence that the stimulation timing plays a crucial role in tDCS application and it confirms the role of the lDLPFC in verbal working memory performance.

Human cytomegalovirus ie2 affects the migration of glioblastoma by mediating the different splicing patterns of RON through hnRNP A2B1 Glioblastoma is the most aggressive intracranial tumor and diffuse migration is the leading cause of death. Recent evidence has indicated that heterogeneous nuclear ribonucleoprotein A2B1 (hnRNP A2B1) is overexpressed in human glioblastoma tissue and enhances glioblastoma invasion in vitro. We found by mass spectrometry that hnRNP A2B1 interacts with human cytomegalovirus (HCMV) immediate early 86 protein (IE86, ie2 gene-encoded) in malignant glioma cells (U87MG) infected with HCMV. However, the role of hnRNP A2 B1 in glioblastoma development remains poorly understood. Here, we report that hnRNP A2B1 is highly expressed in the HCMV·ie2 transgenic mice model. This phenomenon was confirmed in U87MG cell lines transfected with pEGFP-N3-ie2 plasmid. In addition, hnRNP A2B1 knockdown in U87MG cells inhibited tumor migration, and this effect might be mediated by hnRNP A2B1 through effects on splicing patterns of RON. Our data suggested that HCMV· ie2 promotes glioblastoma migration by regulating hnRNP A2B1 expression.

Upregulation of microRNA-205 is a potential biomarker for intracranial aneurysms Inhibition of microRNA-205 is considered to be a therapeutic target for abdominal aortic aneurysm in animal model. Hepatocyte growth factor also plays pivotal roles in the pathogenesis of intracranial aneurysms, and its expression can be regulated by different miRNAs in different processes. We investigated the involvement of microRNA-205 in intracranial aneurysms and explored is potential interaction with hepatocyte growth factor. We found that blood levels of microRNA-205 were significantly higher in patients with intracranial aneurysms than in healthy controls. High blood levels of microRNA-205 showed diagnostic values for intracranial aneurysms. MicroRNA-205 and hepatocyte growth factor were negatively correlated in patients with intracranial aneurysms. MicroRNA-205 overexpression inhibited hepatocyte growth factor expression and reduced cell viability. Therefore, microRNA-205 may participate in intracranial aneurysms and may serve as a diagnostic marker for this disease.

LncRNA SAMMSON overexpression distinguished glioblastoma patients from patients with diffuse neurosarcoidosis The MRI characteristics of diffuse neurosarcoidosis are similar to those of glioblastoma. Therefore, identification of novel biomarkers to distinguish these two diseases is needed. We found that lncRNA Survival Associated Mitochondrial Melanoma-Specific Oncogenic Non-Coding RNA (SAMMSON) was upregulated in plasma of glioblastoma patients but not in diffuse neurosarcoidosis patients comparing to healthy controls. Upregulated SAMMSON distinguished glioblastoma patients from diffuse neurosarcoidosis patients and healthy controls. MiR-622 in glioblastoma patients was inversely correlated with SAMMSON. SAMMSON overexpression caused the downregulated expression of miR-622 in glioblastoma cells, while miR-622 overexpression did not affect SAMMSON expression. SAMMSON overexpression mediated the increased proliferation rate of glioblastoma cells. MiR-622 overexpression played an opposite role and reduced the effects of SAMMSON overexpression. Therefore, plasma SAMMSON has diagnostic value for glioblastoma and SAMMSON overexpression may promote glioblastoma cell proliferation by downregulating miR-622.

Association between imbalance of cortical brain activity and successful motor recovery in sub-acute stroke patients with upper limb hemiparesis: a functional near-infrared spectroscopy study Objective: This study was designed to determine the association between motor functional recovery and interhemispheric imbalance in cortical brain activity in sub-cortical stroke patients with moderate-to-severe upper limb hemiparesis admitted to the convalescent rehabilitation ward. Subjects and methods: The study included first-ever stroke patients with moderate-to-severe upper limb hemiparesis who received multidisciplinary rehabilitation therapy in the rehabilitation ward. Motor function of the affected upper extremity was evaluated by the Fugl-Meyer assessment and action research arm test at 1 (T1) and 3 months (T2) after stroke onset. We also conducted serial functional near-infrared spectroscopy at the same time points and calculated the laterality index, which is based on changes in oxyhaemoglobin in primary sensorimotor cortex (Brodmann Area 4), pre-motor cortex and supplementary motor cortex (PMC + SMA, BA6). Results: The study included eight patients (seven females, mean age: 68.8). Both the Fugl-Meyer assessment and action research arm test scores improved significantly during the study. Laterality index did not change significantly from T1 to T2. There was a no significant correlation between changes in laterality index in each region and improvement in Fugl-Meyer assessment score. In contrast, a significant and negative correlation was noted between ΔLI in Brodmann Area 4 and improvement in action research arm test score. Conclusion: Our results suggested that activation of the non-lesional hemisphere in sub-acute stroke associated with motor recovery in moderate-to-severe upper limb hemiparesis. A multidisciplinary rehabilitation of stroke patients with moderate-to-severe upper limb hemiparesis might enhance the compensatory movements and pre-existing motor network from the non-lesional motor cortex.

Decreased serotonin synthesis is involved in seizure-induced respiratory arrest in DBA/1 mice A known cause of seizure-induced respiratory arrest is the deficiency in serotonergic neurotransmission. Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme of central serotonin (5-hydroxytryptamine) synthesis which converts l-tryptophan to 5-hydroxytryptophan. A recent study revealed a reduction in TPH2 protein expression in the brainstems of DBA/1 mice that developed recurrent seizure-induced respiratory arrest, whereas the activity of this protein was unexplored. Thus this study aims to investigate the association between intrinsic 5-hydroxytryptamine synthesis in the brainstem and the susceptibility for sudden unexpected death in epilepsy in DBA/1 mice. The effect of LY393558, a potent 5-hydroxytryptamine reuptake inhibitor with 5-HT1B/1D receptor antagonist properties, on seizure-induced respiratory arrest evoked by acoustic stimulation was also examined in DBA/1 mice. ELISA results showed significantly decreased TPH2 activity in the brainstems of untreated DBA/1 mice than that of C57BL/6J mice. Moreover, the concentrations of 5-hydroxytryptamine, 5-hydroxytryptophan and 5-HIAA in the brainstems of DBA/1 mice with or without acoustic stimulation were significantly lower than that of C57BL/6J mice. Acute administration of LY393558 also significantly reduced seizure-induced respiratory arrest in DBA/1 mice. These observations provide novel evidences for the hypothesis that 5-hydroxytryptamine deficiency might be a potential cause of seizure-induced respiratory arrest.

Role of exosomes induced by remote ischemic preconditioning in neuroprotection against cerebral ischemia Remote ischemic preconditioning (RIPC) is an effective regimen for neuroprotection in ischemic stroke. Exosomes are extracellular vesicles released into the blood, where they can transfer signals throughout the body. Several studies have demonstrated that RIPC leads to many changes in circulating exosomes. However, the role of RIPC-induced exosomes in neuroprotection remains to be determined. In the current study, we demonstrate that infusion of enriched plasma exosomes from RIPC-treated mice significantly attenuates infarction size in a murine model of cerebral ischemia compared to control group receiving infusion of exosomes from non-RIPC-treated mice. Further studies show that infusion of RIPC-exosomes markedly improves neurological functions. In line with the above findings, we find that the level of hypoxia inducible transcription factor (HIF)-1α is significantly higher in plasma exosomes from mice subjected to RIPC than those from control mice, which could have contributed to the RIPC-exosome-induced neuroprotection through HIF-1α-induced signals including the enhanced tolerance to hypoxia. To our knowledge, this is the first to demonstrate RIPC protects against cerebral ischemia through inducing neuroprotective exosomes.

Physiological arousal and visuocortical connectivity predict subsequent vividness of negative memories Relative to neutral memories, negative and positive memories both exhibit an increase in memory longevity, subjective memory re-experiencing and amygdala activation. These memory enhancements are often attributed to shared influences of arousal on memory. Yet, prior work suggests the intriguing possibility that arousal affects memory networks in valence-specific ways. Psychophysics work has shown that arousal-related heart rate deceleration (HRD) responses are related to enhanced amygdala-visual functional connectivity (AVFC) and visual perception of negative stimuli. However, in the memory realm, it is not known whether the effect of AVFC influences subsequent negative memory outcomes as a function of the magnitude of physiological arousal during encoding. Using psycho-autonomic interaction analyses and trial-level measures of HRD as an objective measure of arousal during encoding of emotional stimuli, our findings suggest that the magnitude of the HRD modulates the effect of AVFC on subsequent negative memory vividness. Specifically, AVFC effects in early visual regions predicted negative memory vividness, not neutral or positive vividness, but only in the presence of heightened physiological arousal. This novel approach was grounded in a replication of prior working showing enhanced HRD effects in the insula for negative stimuli. These findings demonstrate that the effect of arousal on emotional memory networks depends on valence and provide further evidence that negative valence may enhance the incorporation of visuo-sensory regions into emotional memory networks.

Corticospinal excitability related to reciprocal muscles during the motor preparation period: effect of movement repetition Objectives Voluntary movements require a preparatory phase before action initiation to elaborate optimal motor commands. This study investigated the time course of change in corticospinal excitability related to each agonist or antagonist muscle during the motor preparation period and the influence of movement repetition on time course change in corticospinal excitability. Methods The participants were instructed to perform wrist flexion as quickly as possible in response to the appearance of a red circle. One hundred fifty milliseconds after the presentation of the red circle cue, we delivered transcranial magnetic stimulation at the primary motor cortex related to the agonist flexor and the antagonist extensor carpi radialis muscles. Results The motor evoked potential amplitudes for both the flexor and extensor carpi radialis during the motor preparation period which were regressed on the logarithm of time, and there were no significant differences in the slope of the logarithmic curves in the early half trials of movement repetition. However, the slope of the logarithmic curve of the flexor carpi radialis was steeper than that of the extensor carpi radialis in the late half trials of movement repetition. Conclusion These results implied that corticospinal excitability for agonist muscles during the motor preparation period is consistently modulated by movement repetition, whereas that for antagonist muscles is weakened by movement repetition.

Scene processing following damage to the ventromedial prefrontal cortex It has been suggested that the mental construction of scene imagery is a core process underpinning functions such as autobiographical memory, future thinking and spatial navigation. Damage to the ventromedial prefrontal cortex in humans can cause deficits in all of these cognitive domains. Moreover, it has also been reported that patients with ventromedial prefrontal cortex lesions are impaired at imagining fictitious scenes, although they seem able to describe specific scenes from autobiographical events. In general, not much is known about how ventromedial prefrontal cortex patients process scenes. Here, we deployed a recently-developed task to provide insights into this issue, which involved detecting either semantic (e.g. an elephant with butterflies for ears) or constructive (e.g. an endless staircase) violations in scene images. Identifying constructive violations typically provokes the formation of internal scene models in healthy control participants. We tested patients with bilateral ventromedial prefrontal cortex damage, brain-damaged control patients and healthy control participants. We found no evidence for statistically significant differences between the groups in detecting either type of violation. These results suggest that an intact ventromedial prefrontal cortex is not necessary for some aspects of scene processing, with implications for understanding its role in functions such as autobiographical memory and future thinking.