Enhancement of low gamma oscillations by volitional conditioning of local field potential in the primary motor and visual cortex of mice.

Volitional control of local field potential oscillations in low gamma band via brain machine interface can not only uncover the relationship between low gamma oscillation and neural synchrony but also suggest a therapeutic potential to reverse abnormal local field potential oscillation in neurocognitive disorders. In nonhuman primates, the volitional control of low gamma oscillations has been demonstrated by brain machine interface techniques in the primary motor and visual cortex. However, it is not clear whether this holds in other brain regions and other species, for which gamma rhythms might involve in highly different neural processes. Here, we established a closed-loop brain-machine interface and succeeded in training mice to volitionally elevate low gamma power of local field potential in the primary motor and visual cortex. We found that the mice accomplished the task in a goal-directed manner and spiking activity exhibited phase-locking to the oscillation in local field potential in both areas. Moreover, long-term training made the power enhancement specific to direct and adjacent channel, and increased the transcriptional levels of NMDA receptors as well as that of hypoxia-inducible factor relevant to metabolism. Our results suggest that volitionally generated low gamma rhythms in different brain regions share similar mechanisms and pave the way for employing brain machine interface in therapy of neurocognitive disorders.

Non-invasive auditory and visual stimulation attenuates α-Synuclein deposition and improves motor and non-motor symptoms in PD mice.

Parkinson's disease (PD) is characterized by dopaminergic neuron loss and α-synuclein (α-Syn) aggregates, but lacks effective treatments for the disease progression and non-motor symptoms. Recently, combined 40 Hz auditory and visual stimulation is emerging as a promising non-invasive method to decrease amyloid and improve cognition in Alzheimer's disease (AD), but whether this treatment can modify α-Syn-induced PD pathology remains unclear. Here we evaluated the effects of chronic exposure to 40 Hz and 80 Hz auditory and visual stimulation on α-Syn accumulation and the functional effects of 40 Hz stimulation on motor, cognitive and mood dysfunctions in PD mice. We found that 40 Hz and 80 Hz auditory and visual stimulation activated multiple cortical regions, entrained gamma oscillations and markedly attenuated p-α-Syn deposition in neurons, but not astrocytes, microglial cells in the primary and secondary motor cortex (M1, M2), medial prefrontal cortex (mPFC) and the striatum. Moreover, 40 Hz stimulation significantly reduced cell apoptosis in M1, increased the neuromuscular strength selectively in PD mice, which correlated with p-α-Syn reduction in the motor cortex. In addition, 40 Hz stimulation improved spatial working memory and decreased depressive-like behaviors specifically in PD mice, which correlated with p-α-Syn reduction in mPFC, but promoted anxiety-like behaviors and increased stress-related adreno-cortico-tropic-hormone (ACTH), corticosterone levels in the plasma of normal mice. Collectively, we demonstrated that chronic multisensory gamma stimulation (40 Hz and 80 Hz) significantly attenuates α-Syn deposition in neurons of the interconnected cortex and 40 Hz stimulation improved neuromuscular strength, spatial working memory, and reduced depressive behaviors, which support its non-invasive therapeutic potential for modifying PD progression and treating non-motor symptoms.

Sensory eye dominance following surgically correction for acute acquired concomitant esotropia of adulthood.

BACKGROUND: Acute acquired concomitant esotropia (AACE) is an unusual presentation characterized by acute onset of esotropia after infancy. For patients with AACE of adulthood, the outcome of surgery, which is a common treatment, often shows successful recovery of stereopsis. However, whether surgically corrected patients with AACE of adulthood achieved balanced eyes is yet unclear. METHODS: Here, we used a binocular phase combination paradigm to quantitatively assess the ocular dominance of 22 surgically aligned patients with AACE of adulthood, which all had regained normal stereopsis after the surgery and 14 adult controls with normal vision. The sensory eye dominance was quantified as the interocular contrast ratio, termed balance point, at which each eye contributed equally to the perception of cyclopean grating. RESULTS: We found that, normal controls had a mean balance point value close to unity (0.96 ± 0.01), whereas adult AACE patients exhibited apparent interocular imbalance (0.76 ± 0.04), which was significantly different from control group (Mann-Whitney U = 135, P < 0.001, two tailed). In addition, the balance point of adults with AACE didn't correlate with the interval between onset of esotropia and the surgery (r = - 0.262, p = 0.239), or the length of postoperative follow-up period (r = 0.127, p = 0.575). CONCLUSION: Our results suggest that, for patients with AACE of adulthood whose eyes had been straightened, there is still residual sensory imbalance which may be a potential risk factor for AACE of adulthood.

Accumbal adenosine A2A receptor inactivation biases for large and costly rewards in the effort- but not delay-based decision making.

The cost-benefit decision-making (CBDM) is critical to normal human activity and a diminished willingness to expend effort to obtain rewards is a prevalent/noted characteristic of neuropsychiatric disorders such as schizophrenia, Parkinson's disease. Numerous studies have identified nucleus accumbens (NAc) as an important locus for CBDM control but their neuromodulatory and behavioral mechanisms remain largely under-explored. Adenosine A2A receptors (A2ARs), which are highly concentrated in the striatopallidal neurons, can integrate glutamate and dopamine signals for controlling effort-related choice behaviors. While the involvement of A2ARs in effort-based decision making is well documented, the role of other decision variables (reward discrimination) in effort-based decision making and the role of A2AR in delay-based decision making are less clear. In this study, we have developed a well-controlled CBDM behavioral paradigm to manipulate effort/cost and reward independently or in combination, allowing a dissection of four behavioral elements: effort-based CBDM (E-CBDM), delay-based CBDM (D-CBDM), reward discrimination (RD), effort discrimination (ED), and determined the effect of genetic knockdown (KD) of NAc A2AR on the four behavioral elements. We found that A2AR KD in NAc increased the choice for larger, more costly reward in the E-CBDM, but not D-CBDM. Furthermore, this high-effort/high-reward bias was attributable to the increased willingness to engage in effort but not the effect of discrimination of reward magnitude. Our findings substantiate an important role of the NAc A2AR in control of E-CBDM and support that pharmacologically targeting NAc A2ARs would be a useful strategy for treating the aberrant effort-based decision making in neuropsychiatric disorders.

Effects of putrescine on the quality and epigenetic modification of mouse oocytes during in vitro maturation.

CONTEXT: Low ovarian putrescine levels and decreased peak values following luteinising hormone peaks are related to poor oocyte quantity and quality in ageing women. AIMS: To investigate the effects of putrescine supplementation in in vitro maturation (IVM) medium on oocyte quality and epigenetic modification. METHODS: Germinal vesicle oocytes retrieved from the ovaries of 8-week-old and 9-month-old mice were divided into four groups (the young, young+difluoromethylornithine (DFMO), ageing and ageing+putrescine groups) and cultured in IVM medium with or without 1mM putrescine or DFMO for 16h. The first polar body extrusion (PBE), cleavage and embryonic development were evaluated. Spindles, chromosomes, mitochondria and reactive oxygen species (ROS) were measured. The expression levels of SIRT1, H3K9ac, H3K9me2, H3K9me3, and 5mC levels were evaluated. Sirt1 and imprinted genes were detected. RESULTS: The PBE was higher in the ageing+putrescine group than in the ageing group. Putrescine increased the total and inner cell mass cell numbers of blastocysts in ageing oocytes. Putrescine decreased aberrant spindles and chromosome aneuploidy, increased the mitochondrial membrane potential and decreased ROS levels. Putrescine increased SIRT1 expression and attenuated the upregulation of H3K9ac levels in ageing oocytes. Putrescine did not affect 5mC, H3K9me2 or H3K9me3 levels or imprinted gene expression. CONCLUSIONS: Putrescine supplementation during IVM improved the maturation and quality of ageing oocytes and promoted embryonic development by decreasing ROS generation, maintaining mitochondrial and spindle function and correcting aberrant epigenetic modification. IMPLICATIONS: Putrescine shows application potential for human-assisted reproduction, especially for IVM of oocytes from ageing women.

Epigenetic effect of putrescine supplementation during in vitro maturation of oocytes on offspring in mice.

PURPOSE: To investigate the epigenetic safety of putrescine supplementation during in vitro maturation (IVM) to offspring. METHODS: Germinal vesicle oocytes retrieved from 12-week-old mice were randomly divided into two groups and cultured in IVM medium with or without 1 mmol/L putrescine for 16 h. Then, in vitro fertilization and embryo transplantation were conducted to produce the F1 offspring. The F1 mated with ordinary mice and bred the F2 offspring. The DNA methylation patterns in the brain and heart of F1 were investigated by reduced representation bisulfite sequencing. Imprinted gene expression levels of F1 oocytes were tested. The global methylation of F2 was examined by dot blot. RESULTS: The weight, organ coefficient, and histology were normal in the F1 and F2 offspring from the putrescine-treated oocytes. An overall methylation level of 31.23 to 32.53% was observed for all CpG sites in the brain and heart of the two groups. The DNA methylation patterns of the brain and heart in F1 were not altered in general, with subtle differences. The expression levels of imprinted genes including H19, Snrpn, Peg3, Igf2, and Igf2r did not statistically change. The global 5mC level of F2 was consistent with the control group. CONCLUSION: Putrescine supplementation during IVM did not directly affect the development, health, and reproduction, and did not affect the genome and global epigenetics of mouse offspring derived from those oocytes. The transient putrescine treatment for improving oocyte maturation shows its long-term safety of genome and epigenetics in the offspring of mice.

The Early Diagnostic Value of Procalcitonin in Pneumonia After Off-Pump Coronary Artery Bypass Grafting Surgery.

BACKGROUND The incidence of early postoperative pneumonia (EPOP) after off-pump coronary artery bypass grafting surgery (CABG) is relatively high, but its diagnosis by traditional methods remains difficult, which could be deleterious to the prognosis. Moreover, few data exist regarding procalcitonin (PCT) in early diagnosis of pneumonia after off-pump CABG. Thus, this study was performed to evaluate the value of PCT in diagnosing EPOP after off-pump CABG. MATERIAL AND METHODS A total of 402 consecutive patients undergoing off-pump CABG were retrospectively enrolled. Forty-four patients were diagnosed with EPOP and 112 patients were diagnosed with systemic inflammatory response syndrome (SIRS). Chest roentgenogram, serum PCT, white blood cells, neutral granulocyte ratio, and daily maximum body temperature were recorded. The ability of PCT to diagnose EPOP was evaluated by receiver operating characteristic (ROC) analyses in comparison with traditional methods. Clinical net benefits were estimated via decision curve analysis (DCA). RESULTS PCT presented satisfying accuracy in diagnosing EPOP with a cutoff value of 1.585 ng/mL (area under the curve [AUC] 0.808, 95% confidence interval [CI] 0.724-0.891, sensitivity 73%, specificity 86%). PCT performed better in diagnosing EPOP among SIRS patients (AUC 0.868, 95% CI 0.748-0.988, sensitivity 85%, specificity 89%). DCA showed valuable clinical net benefits of PCT in diagnosing EPOP after off-pump CABG regardless of threshold selected. CONCLUSIONS PCT could be a diagnostic marker for EPOP after off-pump CABG. The optimal cutoff value for diagnosing EPOP was 1.585 ng/mL. The application of PCT in diagnosing EPOP in SIRS patients was also satisfying with a cutoff value of 1.775 ng/mL.

High-sensitivity troponin T release profile in off-pump coronary artery bypass grafting patients with normal postoperative course.

BACKGROUND: The aim of the study was to investigate the high-sensitivity troponin T (hs-TnT) release profile in off-pump coronary artery bypass grafting (OPCABG) patients with normal postoperative course. METHODS: From January 2015 to October 2016, 398 consecutive OPCABG patients who had normal postoperative courses were enrolled. Blood samples for hs-TnT were collected at several time points and the comparisons among different time points grouped by various factors were further analyzed. RESULTS: There were 317 male and 81 female patients, with a median age of 64. For 66.1% of the patients, peak hs-TnT occurred at the 24th hour after OPCABG, regardless of the groups divided by different factors. In total, the hs-TnT values were much higher in male group (P = 0.035), in patients who need 5 or more bypass grafts (P = 0.035) and in patients with high-risk EuroSCORE II assessment (P = 0.013). However, we failed to find any significant differences between different age groups (P = 0.129) or among different coronary heart disease classifications (P = 0.191). CONCLUSIONS: The hs-TnT values were affected by various factors and culminated around the first 24 h following OPCABG. It may provide some useful information for future clinical studies of myocardial biomarkers after OPCABG.