A paleo-neurologic investigation of the social brain hypothesis in frontotemporal dementia.

The social brain hypothesis posits that a disproportionate encephalization in primates enabled to adapt behavior to a social context. Also, it has been proposed that phylogenetically recent brain areas are disproportionally affected by neurodegeneration. Using structural and functional magnetic resonance imaging, the present study investigates brain-behavior associations and neural integrity of hyperspecialized and domain-general cortical social brain areas in behavioral variant frontotemporal dementia (bvFTD). The results revealed that both structure and function of hyperspecialized social areas in the middle portion of the superior temporal sulcus (STS) are compromised in bvFTD, while no deterioration was observed in domain general social areas in the posterior STS. While the structural findings adhered to an anterior-posterior gradient, the functional group differences only occurred in the hyperspecialized locations. Activity in specialized regions was associated with structural integrity of the amygdala and with social deficits in bvFTD. In conclusion, the results are in line with the paleo-neurology hypothesis positing that neurodegeneration primarily hits cortical areas showing increased specialization, but also with the compatible alternative explanation that anterior STS regions degenerate earlier, based on stronger connections to and trans-neuronal spreading from regions affected early in bvFTD.

Precision Seeding Compensation and Positioning Based on Multisensors.

The current multi-row planter always leads to uneven seeding spacing between rows while seeding in curve paths, which causes uneven growth, a cost increase of production and management, and reduced yield. With the development of smart farming technology, a curve seeding compensation and precise positioning model is proposed in the paper to calculate the real-time speed and position of each seeding unit based on the information from multisensors, such as GNSS and IMU, and to predict the next seeding position to achieve uniform seeding on the curve and improve the unit yield of crops. MATLAB Simulink simulation experiments show that the seeding pass rate of the model is 99.97% when the positioning accuracy is ±0.01 m and the traction speed is 1 m/s, and the seeding pass rate of the five-row seeder is as high as 99.81% when the traction speed is 3 m/s, which verifies the effectiveness and practicality of the model.

Neurobiological substrates of major psychiatry disorders: transdiagnostic associations between white matter abnormalities, neuregulin 1 and clinical manifestation.

Background: Schizophrenia, bipolar disorder and major depressive disorder are increasingly being conceptualized as a transdiagnostic continuum. Disruption of white matter is a common alteration in these psychiatric disorders, but the molecular mechanisms underlying the disruption remain unclear. Neuregulin 1 (NRG1) is genetically linked with susceptibility to schizophrenia, bipolar disorder and major depressive disorder, and it is also related to white matter. Methods: Using a transdiagnostic approach, we aimed to identify white matter differences associated with NRG1 and their relationship to transdiagnostic symptoms and cognitive function. We examined the white matter of 1051 participants (318 healthy controls and 733 patients with major psychiatric disorders: 254 with schizophrenia, 212 with bipolar disorder and 267 with major depressive disorder) who underwent diffusion tensor imaging. We measured the plasma NRG1-ß1 levels of 331 participants. We also evaluated clinical symptoms and cognitive function. Results: In the patient group, abnormal white matter was negatively associated with NRG1-ß1 levels in the genu of the corpus callosum, right uncinate fasciculus, bilateral inferior fronto-occipital fasciculus, right external capsule, fornix, right optic tract, left straight gyrus white matter and left olfactory radiation. These NRG1-associated white matter abnormalities were also associated with depression and anxiety symptoms and executive function in patients with a major psychiatric disorder. Furthermore, across the 3 disorders we observed analogous alterations in white matter, NRG1-ß1 levels and clinical manifestations. Limitations: Medication status, the wide age range and our cross-sectional findings were limitations of this study. Conclusion: This study is the first to provide evidence for an association between NRG1, white matter abnormalities, clinical symptoms and cognition in a transdiagnostic psychiatric cohort. These findings provide further support for an understanding of the molecular mechanisms that underlie the neuroimaging substrates of major psychiatric disorders and their clinical implications.

Amplitude of low-frequency fluctuation (ALFF) may be associated with cognitive impairment in schizophrenia: a correlation study.

BACKGROUND: Cognitive impairments are prominent in schizophrenia (SZ). Imaging studies have demonstrated that functional changes of several areas of the brain exist in SZ patients. The relationships between these two indexes are largely unexplored in SZ. The MATRICS Consensus Cognitive Battery (MCCB) was used to measure cognitive impairment in multi-dimensional cognitive fields of SZ patients. This study was conducted to explore the relationship between cognitive functional impairment and the amplitude of low-frequency fluctuation (ALFF) in SZ patients. METHOD: A total of 104 participants (44 SZ patients and 60 age- and gender-matched healthy controls (HC)) were recruited for this study. The MCCB was used to assess cognitive function of the participants, while brain activity was assessed using the ALFF. The relationship between the MCCB and the ALFF was investigated by using a correlation analysis. RESULTS: There were significant differences between SZ patients and HC in MCCB total and domain scores as well as in ALFF results. The reduction of ALFF in the bilateral postcentral gyri and paracentral lobule in SZ patients has a negative correlation with the MCCB sub-test of symbol coding. CONCLUSION: These findings suggest that the reduction of ALFF in bilateral postcentral gyri and paracentral lobule may be related to cognitive impairment in SZ patients.

Prelithiated rigid polymer with high ionic conductivity as silicon-based anode binder for lithium-ion battery.

Silicon-based electrodes suffer from rapid performance degradation derived from a severe volume expansion during cycling in lithium-ion batteries, and using elaborately designed polymer binders is deemed an efficient tactic to tackle the above thorny issues. In this study, a water-soluble rigid-rod poly(2,2'-disulfonyl-4,4'-benzidine terephthalamide) (PBDT) polymer is described and employed as the binder for Si-based electrodes for the first time. The nematic rigid PBDT bundles wrapped around the Si nanoparticles by hydrogen bonding effectively inhibit the volume expansion of the Si and promote the formation of stable solid electrolyte interfaces (SEI). Moreover, the prelithiated PBDT binder with high ionic conductivity (3.2 × 10-4 S cm-1) not only improves the Li-ions transportation behaviors in the electrode but can also partially compensate for the irreversible Li source consumption during SEI formation. Consequently, the cycling stability and initial coulombic efficiency of the Si-based electrodes with the PBDT binder are remarkably enhanced compared to that with the PVDF binder. This work demonstrates the molecular structure and prelithiation strategy of the polymer binder that play a crucial role in improving the performance of Si-based electrodes with high-volume expansion.

Gender differences in plasma glial cell line-derived neurotrophic factor levels of patients with bipolar disorder.

BACKGROUND: The glial cell line-derived neurotrophic factor (GDNF) has an important role in neurons and is closely associated with psychiatric disorders. The development of bipolar disorder (BD) may differ between genders. Existing studies have shown that plasma GDNF levels are altered in patients with BD. In this study, we investigate whether the GDNF levels in patients with BD differ in terms of gender. METHODS: Participants were divided into the BD group (n = 76, with 26 males and 50 females) and healthy control (HC) group (n = 89, with 35 males and 54 females). Plasma GDNF levels were detected via multifactor assay. Clinical symptoms of patients with BD were collected and assessed using the Hamilton Depression-17 Inventory, Hamilton Anxiety-17 Inventory, Young's Mania Rating Scale, and Brief Psychiatric Rating Scale. RESULTS: The GDNF levels were significantly higher in all participants in the HC group (F = 4.262, p < 0.05) compared with those in the BD group. In the HC group, the males (t = 4.814, p < 0.001) presented significantly higher levels than the females. The plasma GDNF levels in males in the BD group (t = 3.022, p < 0.05) were significantly lower than those in males in the HC group. CONCLUSION: Differences in plasma GDNF levels are associated with the gender of patients with BD.

Neural compensation in manifest neurodegeneration: systems neuroscience evidence from social cognition in frontotemporal dementia.

BACKGROUND: It has been argued that symptom onset in neurodegeneration reflects the overload of compensatory mechanisms. The present study aimed to investigate whether neural functional compensation can be observed in the manifest neurodegenerative disease stage, by focusing on a core deficit in frontotemporal dementia, i.e. social cognition, and by combining psychophysical assessment, structural MRI and functional MRI with multidimensional neural markers that allow quantification of neural computations. METHODS: Nineteen patients with clinically manifest behavioral variant frontotemporal dementia (bvFTD) and 20 controls performed facial expression recognition tasks in the MRI-scanner and offline. Group differences in grey matter volume, neural response amplitude and neural patterns were assessed via a combination of voxel-wise whole-brain, searchlight, and ROI-analyses and these measures were correlated with psychophysical measures of emotion, valence and arousal ratings. RESULTS: Significant group effects were observed only outside task-relevant regions, converging in the caudate nucleus. This area showed a diagnostic neural pattern as well as hyperactivation and stronger neural representation of facial expressions in the bvFTD sample. Furthermore, response amplitude was associated with behavioral arousal ratings. CONCLUSIONS: The combined findings reveal converging support for compensatory processes in clinically manifest neurodegeneration, complementing accounts that clinical onset synchronizes with the breakdown of compensatory processes. Furthermore, active compensation may proceed along nodes in intrinsically connected networks, rather than along the more task-specific networks. The findings underscore the potential of distributed multidimensional functional neural characteristics that may provide a novel class of biomarkers with both diagnostic and therapeutic implications, including biomarkers for clinical trials.

Qi-Tai-Suan, an oleanolic acid derivative, ameliorates ischemic heart failure via suppression of cardiac apoptosis, inflammation and fibrosis.

Although anti-thrombotic therapy has been successful for prevention of deaths from acute myocardial infarction (MI), by far, there are few preventive and therapeutic options for ischemic heart failure (IHF) after MI. Qi-Tai-Suan (QTS) is an oleanolic acid (OA) derivative which once underwent a clinical trial for treating hepatitis. In this study, we investigated the potential cardioprotective effect of QTS on IHF. IHF mouse model was constructed by coronary artery ligation in male C57BL/6J mice, and the protective effects of QTS on IHF were examined by echocardiography measurement, histological and TUNEL analysis, etc. We found that QTS exhibited promising cardioprotective effect on IHF. QTS treatment significantly improved cardiac function of IHF mice and the symptoms of heart failure. Notably, QTS had much better oral bioavailability (F = 41.91%) in mice than its parent drug OA, and took effects mainly as its original form. Mechanistically, QTS ameliorated ischemic heart failure likely through suppression of cardiac apoptosis, inflammation and fibrosis. Taken together, QTS holds great promise as a preventive and therapeutic agent for ischemic heart failure and related diseases.

The role of leptin in indirectly mediating "somatic anxiety" symptoms in major depressive disorder.

Background: Leptin is a multifunctional hormone secreted from adipose tissue, which plays a core role in regulating energy intake and expenditure. Evidence has demonstrated that leptin receptors are located in brain areas involved in emotional processing, and major depressive disorder (MDD) is characterized by dysfunction of emotional processing. Taken together, these features suggest that leptin may play a potential role in the pathophysiology of MDD. However, the precise roles of leptin in modulating depressive symptoms in MDD remain unclear. Methods: Participants [18 drug-naïve MDD patients, 15 unaffected first-degree relatives of MDD patients (FDR-MDD), and 40 healthy controls] completed clinical assessments and provided blood samples for measurement of leptin levels. We evaluated the effect of leptin on clinical status (MDD or FDR-MDD) and symptomatic dimensionalities of MDD using mediation analysis. Results: We found that leptin was increased in MDD patients and this only predicted "somatic anxiety" symptoms. Furthermore, leptin was a significant and indirect mediator of the association between clinical status (MDD or FDR-MDD) and "somatic anxiety" symptoms. Conclusion: Our finding that leptin was a significant and indirect mediator of clinical status (MDD or FDR-MDD) and "somatic anxiety" symptoms suggests that leptin may indirectly affect somatic depressive symptoms in MDD. Our findings may provide a theoretical basis for novel clinical interventions in MDD.

Persistent lentivirus infection induces early myeloid suppressor cells expansion to subvert protective memory CD8 T cell response✰,✰✰.

BACKGROUND: Memory CD8+T cell responses play an essential role in protection against persistent infection. However, HIV-1 evades vaccine-induced memory CD8+T cell response by mechanisms that are not fully understood. METHODS: We analyzed the temporal dynamics of CD8+T cell recall activity and function during EcoHIV infection in a potent PD1-based vaccine immunized immunocompetent mice. FINDINGS: Upon intraperitoneal EcoHIV infection, high levels of HIV-1 GAG-specific CD8+T lymphocytes recall response reduced EcoHIV-infected cells significantly. However, this protective effect diminished quickly after seven days, followed by a rapid reduction of GAG-specific CD8+T cell number and activity, and viral persistence. Mechanistically, EcoHIV activated dendritic cells (DCs) and myeloid cells. Myeloid cells were infected and rapidly expanded, exhibiting elevated PD-L1/-L2 expression and T cell suppressive function before day 7, and were resistant to CD8+T cell-mediated apoptosis. Depletion of myeloid-derived suppressor cells (MDSCs) reduced EcoHIV infection and boosted T cell responses. INTERPRETATION: This study provides an overview of the temporal interplay of persistent virus, DCs, MDSCs and antigen-specific CD8+T cells during acute infection. We identify MDSCs as critical gatekeepers that restrain antiviral T cell memory responses, and highlight MDSCs as an important target for developing effective vaccines against chronic human infections. FUNDING: Hong Kong Research Grant Council (T11-709/18-N, HKU5/CRF/13G), General Research Fund (17122915 and 17114114), Hong Kong Health and Medical Research Fund (11100752, 14130582, 16150662), Grant RGC-ANR A-HKU709/14, the San-Ming Project of Medicine (SZSM201512029), University Development Fund of the University of Hong Kong and Li Ka Shing Faculty of Medicine Matching Fund to HKU AIDS Institute.

Decreased plasma glial cell line-derived neurotrophic factor level in major depressive disorder is associated with age and clinical severity.

BACKGROUND: Glial cell line-derived neurotrophic factor (GDNF) as a neurotrophic factor closely related to depression is able to promote the growth, proliferation, differentiation, and survival of multiple neurons. Clinical features, recurrence rates and suicide rates are significant different in major depressive disorder (MDD) according to age. GDNF level changes in the peripheral blood has been reported in patients with MDD. In this study, we aimed to investigate whether GDNF levels differentiated within various age groups and its relationship with age/clinical severity. METHOD: MDD subjects and healthy controls (HC) are divided into younger (age 13-24 years) group (yMDD n = 35, yHC n = 44) and older (age 25-45 years) group (oMDD n = 30, oHC n = 55) based on the age of brain maturity. Clinical symptom severity was evaluated by the Hamilton Depression Rating Scale (HAMD-17) and the Hamilton Anxiety Rating Scale (HAMA-17). The levels of plasma GDNF were compared within subgroups. RESULTS: Plasma GDNF levels in yMDD patients were significantly decreased compared to yHC (yMDD 1.55 ±â€¯0.46pg/ml, yHC 1.77 ±â€¯0.47pg/ml, p < 0.05). Moreover, such difference was not found between oMDD group and oHC group. Our results also showed negative correlations between plasma GDNF levels and HAMD/HAMA scores (r = -0.33, p < 0.05; r = -0.39, p < 0.05). LIMITATIONS: This study was underpowered to observe dynamic changes between age and GDNF in MDD due to the cross-sectional design of present study. We also failed to divided subjects into more age groups because of moderate sample size. CONCLUSION: The present result showed the level of protective neurotrophic factor GDNF associated with age in MDD, suggesting a relevance between GDNF and MDD subjects abnormal brain development in adolescent and young adult period.

Abnormal Functional and Structural Connectivity of Amygdala-Prefrontal Circuit in First-Episode Adolescent Depression: A Combined fMRI and DTI Study.

BACKGROUND: Abnormalities of functional and structural connectivity in the amygdala-prefrontal circuit which involved with emotion processing have been implicated in adults with major depressive disorder (MDD). Adolescent MDD may have severer dysfunction of emotion processing than adult MDD. In this study, we used resting-state functional magnetic resonance imaging (rs-fMRI) and diffusion tensor imaging (DTI) to examine the potential functional and structural connectivity abnormalities within amygdala-prefrontal circuit in first-episode medication-naïve adolescents with MDD. METHODS: Rs-fMRI and DTI data were acquired from 36 first-episode medication-naïve MDD adolescents and 37 healthy controls (HC). Functional connectivity between amygdala and the prefrontal cortex (PFC) and fractional anisotropy (FA) values of the uncinate fasciculus (UF) which connecting amygdala and PFC were compared between the MDD and HC groups. The correlation between the FA value of UF and the strength of the functional connectivity in the PFC showing significant differences between the two groups was identified. RESULTS: Compared with the HC group, decreased functional connectivity between left amygdala and left ventral PFC was detected in the adolescent MDD group. FA values were significant lower in the left UF within the adolescent MDD group compared to the HC group. There was no significant correlation between the UF and FA, and the strength of functional connectivity within the adolescent MDD group. CONCLUSIONS: First-episode medication-naïve adolescent MDD showed decreased functional and structural connectivity in the amygdala-prefrontal circuit. These findings suggest that both functional and structural abnormalities of the amygdala-prefrontal circuit may present in the early onset of adolescent MDD and play an important role in the neuropathophysiology of adolescent MDD.