Beta-band power modulation in the human amygdala differentiates between go/no-go responses in an arm-reaching task.

Objective. Traditionally known for its involvement in emotional processing, the amygdala's involvement in motor control remains relatively unexplored, with sparse investigations into the neural mechanisms governing amygdaloid motor movement and inhibition. This study aimed to characterize the amygdaloid beta-band (13-30 Hz) power between 'Go' and 'No-go' trials of an arm-reaching task.Approach. Ten participants with drug-resistant epilepsy implanted with stereoelectroencephalographic (SEEG) electrodes in the amygdala were enrolled in this study. SEEG data was recorded throughout discrete phases of a direct reach Go/No-go task, during which participants reached a touchscreen monitor or withheld movement based on a colored cue. Multitaper power analysis along with Wilcoxon signed-rank and Yates-correctedZtests were used to assess significant modulations of beta power between the Response and fixation (baseline) phases in the 'Go' and 'No-go' conditions.Main results. In the 'Go' condition, nine out of the ten participants showed a significant decrease in relative beta-band power during the Response phase (p⩽ 0.0499). In the 'No-go' condition, eight out of the ten participants presented a statistically significant increase in relative beta-band power during the response phase (p⩽ 0.0494). Four out of the eight participants with electrodes in the contralateral hemisphere and seven out of the eight participants with electrodes in the ipsilateral hemisphere presented significant modulation in beta-band power in both the 'Go' and 'No-go' conditions. At the group level, no significant differences were found between the contralateral and ipsilateral sides or between genders.Significance.This study reports beta-band power modulation in the human amygdala during voluntary movement in the setting of motor execution and inhibition. This finding supplements prior research in various brain regions associating beta-band power with motor control. The distinct beta-power modulation observed between these response conditions suggests involvement of amygdaloid oscillations in differentiating between motor inhibition and execution.

Beta-band power classification of go/no-go arm-reaching responses in the human hippocampus.

Objective.Can we classify movement execution and inhibition from hippocampal oscillations during arm-reaching tasks? Traditionally associated with memory encoding, spatial navigation, and motor sequence consolidation, the hippocampus has come under scrutiny for its potential role in movement processing. Stereotactic electroencephalography (SEEG) has provided a unique opportunity to study the neurophysiology of the human hippocampus during motor tasks. In this study, we assess the accuracy of discriminant functions, in combination with principal component analysis (PCA), in classifying between 'Go' and 'No-go' trials in a Go/No-go arm-reaching task.Approach.Our approach centers on capturing the modulation of beta-band (13-30 Hz) power from multiple SEEG contacts in the hippocampus and minimizing the dimensional complexity of channels and frequency bins. This study utilizes SEEG data from the human hippocampus of 10 participants diagnosed with epilepsy. Spectral power was computed during a 'center-out' Go/No-go arm-reaching task, where participants reached or withheld their hand based on a colored cue. PCA was used to reduce data dimension and isolate the highest-variance components within the beta band. The Silhouette score was employed to measure the quality of clustering between 'Go' and 'No-go' trials. The accuracy of five different discriminant functions was evaluated using cross-validation.Main results.The Diagonal-Quadratic model performed best of the 5 classification models, exhibiting the lowest error rate in all participants (median: 9.91%, average: 14.67%). PCA showed that the first two principal components collectively accounted for 54.83% of the total variance explained on average across all participants, ranging from 36.92% to 81.25% among participants.Significance.This study shows that PCA paired with a Diagonal-Quadratic model can be an effective method for classifying between Go/No-go trials from beta-band power in the hippocampus during arm-reaching responses. This emphasizes the significance of hippocampal beta-power modulation in motor control, unveiling its potential implications for brain-computer interface applications.

Correlation between vessel density and thickness in the retina and choroid of severe non-proliferative diabetic retinopathy patients.

Objectives: To explore the correlation between the vessel density (VD) of the retina and choroid vascular plexuses and the thicknesses of their respective retinal layers and choroid membranes in participants with severe non-proliferative diabetic retinopathy (NPDR). Methods: We retrospectively analyzed the data of 42 eyes of 42 participants with diabetes mellitus (DM) and severe NPDR. In addition, 41 eyes of 41 healthy controls were evaluated. Measurements were taken for both groups using optical coherence tomography angiography (OCTA), including the area and perimeter of the foveal vascular zone (FAZ) and the vascular density (VD) in the superficial capillary plexus (SCP), deep capillary plexus (DCP), and choroid capillary (CC). These measurements were compared with the retinal thickness (RT) of the inner/intermediate retinal layers and choroidal thickness (CT). The study evaluated the correlation between RT or CT and VD in the respective vascular networks, namely superficial capillary plexus (SCP), deep capillary plexus (DCP), or CC. Results: The inner RT and VD in all plexuses were significantly lower in the severe NPDR group than in the healthy controls. Furthermore, the FAZ area and perimeter were larger in the severe NPDR group. Inner RT was correlated with VD in the SCP group (r=0.67 and r=0.71 in the healthy control and severe NPDR groups, respectively; p<0.05). CT negatively correlated with VD in the CC (r=-0.697 and r=-0.759 in the healthy control and severe NPDR groups, respectively; p<0.05). Intermediate RT significantly correlated with VD in the DCP of the severe NPDR group (r=-0.55, p<0.05), but not in the healthy control group. Conclusions: Retinal or choroidal thickness strongly correlated with VD. Therefore, patients with severe NPDR must consider the distinct anatomical and functional entities of the various retinal layers and the choroid.

Relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment.

PURPOSE: To assess the relationship between visual acuity and OCT angiography parameters in diabetic retinopathy eyes after treatment, and to analyze the relative factors in PDR eyes. METHODS: A total of 89 eyes, including 42 eyes with non-PDR (NPDR), and 47 eyes after vitrectomy with PDR were included and underwent OCTA. All images were processed by Python or FIJI. Multivariable linear regression models were used to analyze the associations between postoperative BCVA and OCTA parameters in PDR patients. RESULTS: Postoperative OCTA parameters including deep capillary plexus (DCP) parafoveal and perifoveal vessel density (VD), DCP parafoveal and perifoveal vessel length density (VLD), DCP fractal dimension (FD), choriocapillaris plexus (CCP) VD, CCP VLD, were significantly lower in the PDR group than in the NPDR group. In the superficial capillary plexus (SCP), we found a negative correlation between the postoperative BCVA and VD (parafovea: ß coefficient = -0.351, p = 0.023; perifovea: ß coefficient = -0.338, p = 0.036). Perifoveal VLD (ß coefficient = -0.343, p = 0.031) and FD (ß coefficient = -0.375, p = 0.016) of the SCP were also negatively correlated with postoperative BCVA. Regarding the DCP, perifoveal VD (ß coefficient = -0.396, p = 0.008), perifoveal VLD (ß coefficient = -0.334, p = 0.025), vessel tortuosity (VT) (ß coefficient = -0.369, p = 0.015) were negatively correlated with postoperative BCVA. In CCP, VLD (ß coefficient = -0.373, p = 0.023) and number of flow voids (ß coefficient = -0.334, p = 0.036) exhibited a negative association with postoperative BCVA. CONCLUSIONS: Postoperative BCVA of PDR patients was related to OCTA parameters of the SCP (parafoveal and perifoveal VD, perifoveal VLD and FD), DCP (perifoveal VD, VLD, and VT) and CCP (VLD and number of flow voids).

Barocaloric Effects in Dialkylammonium Halide Salts.

Barocaloric effects─solid-state thermal changes induced by the application and removal of hydrostatic pressure─offer the potential for energy-efficient heating and cooling without relying on volatile refrigerants. Here, we report that dialkylammonium halides─organic salts featuring bilayers of alkyl chains templated through hydrogen bonds to halide anions─display large, reversible, and tunable barocaloric effects near ambient temperature. The conformational flexibility and soft nature of the weakly confined hydrocarbons give rise to order-disorder phase transitions in the solid state that are associated with substantial entropy changes (>200 J kg-1 K-1) and high sensitivity to pressure (>24 K kbar-1), the combination of which drives strong barocaloric effects at relatively low pressures. Through high-pressure calorimetry, X-ray diffraction, and Raman spectroscopy, we investigate the structural factors that influence pressure-induced phase transitions of select dialkylammonium halides and evaluate the magnitude and reversibility of their barocaloric effects. Furthermore, we characterize the cyclability of thin-film samples under aggressive conditions (heating rate of 3500 K s-1 and over 11,000 cycles) using nanocalorimetry. Taken together, these results establish dialkylammonium halides as a promising class of pressure-responsive thermal materials.

Chimpanzee adenovirus-mediated multiple gene therapy for age-related macular degeneration.

Neovascular age-related macular degeneration AMD (nAMD) is characterized by choroidal neovascularization (CNV) and could lead to irreversible blindness. However, anti-vascular endothelial growth factor (VEGF) therapy has limited efficacy. Therefore, we generated a chimpanzee adenoviral vector (AdC68-PFC) containing three genes, pigment endothelial-derived factor (PEDF), soluble fms-like tyrosine kinase-1 (sFlt-1), and soluble forms of CD59 (sCD59), to treat nAMD. The results showed that AdC68-PFC mediated a strong onset of PEDF, sFlt-1, and sCD59 expression both in vivo and in vitro. AdC68-PFC showed preventive and therapeutic effects following intravitreal (IVT) injection in the laser-induced CNV model and very low-density lipoprotein receptor-deficient (Vldlr-/-) mouse model. In vitro assessment indicated that AdC68-PFC had a strong inhibitory effect on endothelial cells. Importantly, the safety test showed no evidence of in vivo toxicity of adenovirus in murine eyes. Our findings suggest that AdC68-PFC may be a long-acting and safe gene therapy vector for future nAMD treatments.

Sensory processing deficits and related cortical pathological changes in Alzheimer's disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily affecting cognitive functions. However, sensory deficits in AD start to draw attention due to their high prevalence and early onsets which suggest that they could potentially serve as diagnostic biomarkers and even contribute to the disease progression. This literature review examines the sensory deficits and cortical pathological changes observed in visual, auditory, olfactory, and somatosensory systems in AD patients, as well as in various AD animal models. Sensory deficits may emerge at the early stages of AD, or even precede the cognitive decline, which is accompanied by cortical pathological changes including amyloid-beta deposition, tauopathy, gliosis, and alterations in neuronal excitability, synaptic inputs, and functional plasticity. Notably, these changes are more pronounced in sensory association areas and superficial cortical layers, which may explain the relative preservation of basic sensory functions but early display of deficits of higher sensory functions. We propose that sensory impairment and the progression of AD may establish a cyclical relationship that mutually perpetuates each condition. This review highlights the significance of sensory deficits with or without cortical pathological changes in AD and emphasizes the need for further research to develop reliable early detection and intervention through sensory systems.

Exercise alleviates neovascular age-related macular degeneration by inhibiting AIM2 inflammasome in myeloid cells.

The neovascular form of age-related macular degeneration (nvAMD) is the leading cause of blindness in the elderly population. Vascular endothelial growth factor (VEGF) plays a crucial role in choroidal neovascularization (CNV), and anti-VEGF therapy is recommended as first-line therapy for nvAMD. However, many patients do not radically benefit from this therapy. Epidemiological data suggest that physical exercise is beneficial for many human diseases, including nvAMD. Yet, its protective mechanism and therapeutic potential remain unknown. Here, using clinical samples and mouse models, we found that exercise reduced CNV and enhanced anti-angiogenic therapy efficacy by inhibiting AIM2 inflammasome activation. Furthermore, transfusion of serum from exercised mice transferred the protective effects to sedentary mice. Proteomic data revealed that exercise promoted the release of adiponectin, an anti-inflammatory adipokine from adipose tissue into the circulation, which reduced ROS-mediated DNA damage and suppressed AIM2 inflammasome activation in myeloid cells of CNV eyes through AMPK-p47phox pathway. Simultaneous targeting AIM2 inflammasome product IL-1ß and VEGF produced a synergistic effect for treating choroidal neovascularization. Collectively, this study highlights the therapeutic potential of an exercise-AMD axis and uncovers the AIM2 inflammasome and its product IL-1ß as potential targets for treating nvAMD patients and enhancing the efficacy of anti-VEGF monotherapy.

Colossal barocaloric effects with ultralow hysteresis in two-dimensional metal-halide perovskites.

Pressure-induced thermal changes in solids-barocaloric effects-can be used to drive cooling cycles that offer a promising alternative to traditional vapor-compression technologies. Efficient barocaloric cooling requires materials that undergo reversible phase transitions with large entropy changes, high sensitivity to hydrostatic pressure, and minimal hysteresis, the combination of which has been challenging to achieve in existing barocaloric materials. Here, we report a new mechanism for achieving colossal barocaloric effects that leverages the large volume and conformational entropy changes of hydrocarbon order-disorder transitions within the organic bilayers of select two-dimensional metal-halide perovskites. Significantly, we show how the confined nature of these order-disorder phase transitions and the synthetic tunability of layered perovskites can be leveraged to reduce phase transition hysteresis through careful control over the inorganic-organic interface. The combination of ultralow hysteresis and high pressure sensitivity leads to colossal reversible isothermal entropy changes (>200 J kg-1 K-1) at record-low pressures (<300 bar).

Enrichment analyses identify shared associations for 25 quantitative traits in over 600,000 individuals from seven diverse ancestries.

Since 2005, genome-wide association (GWA) datasets have been largely biased toward sampling European ancestry individuals, and recent studies have shown that GWA results estimated from self-identified European individuals are not transferable to non-European individuals because of various confounding challenges. Here, we demonstrate that enrichment analyses that aggregate SNP-level association statistics at multiple genomic scales-from genes to genomic regions and pathways-have been underutilized in the GWA era and can generate biologically interpretable hypotheses regarding the genetic basis of complex trait architecture. We illustrate examples of the robust associations generated by enrichment analyses while studying 25 continuous traits assayed in 566,786 individuals from seven diverse self-identified human ancestries in the UK Biobank and the Biobank Japan as well as 44,348 admixed individuals from the PAGE consortium including cohorts of African American, Hispanic and Latin American, Native Hawaiian, and American Indian/Alaska Native individuals. We identify 1,000 gene-level associations that are genome-wide significant in at least two ancestry cohorts across these 25 traits as well as highly conserved pathway associations with triglyceride levels in European, East Asian, and Native Hawaiian cohorts.

Regulation of angiotensin II actions by enhancers and super-enhancers in vascular smooth muscle cells.

Angiotensin II (AngII) promotes hypertension and atherosclerosis by activating growth-promoting and pro-inflammatory gene expression in vascular smooth muscle cells (VSMCs). Enhancers and super-enhancers (SEs) play critical roles in driving disease-associated gene expression. However, enhancers/SEs mediating VSMC dysfunction remain uncharacterized. Here, we show that AngII alters vascular enhancer and SE repertoires in cultured VSMCs in vitro, ex vivo, and in AngII-infused mice aortas in vivo. AngII-induced enhancers/SEs are enriched in binding sites for signal-dependent transcription factors and dependent on key signaling kinases. Moreover, CRISPR-Cas9-mediated deletion of candidate enhancers/SEs, targeting SEs with the bromodomain and extra-terminal domain inhibitor JQ1, or knockdown of overlapping long noncoding RNAs (lncRNAs) blocks AngII-induced genes associated with growth-factor signaling and atherosclerosis. Furthermore, JQ1 ameliorates AngII-induced hypertension, medial hypertrophy and inflammation in vivo in mice. These results demonstrate AngII-induced signals integrate enhancers/SEs and lncRNAs to increase expression of genes involved in VSMC dysfunction, and could uncover novel therapies.