Frontiers in Neuroscience

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ISSN / EISSN : 1662-453X / 1662-453X
Published by: Frontiers Media SA (10.3389)
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Maria Alejandra Gonzalez-Gonzalez, Kevin Romero, John Beitter, David Lloyd, Danny V. Lam, Ana Guadalupe Hernandez-Reynoso, Aswini Kanneganti, Han-Kyul Kim, Caroline K. Bjune, Scott Smith, et al.
Frontiers in Neuroscience, Volume 16; https://doi.org/10.3389/fnins.2022.726467

Abstract:
Hypertension is a main cause of death in the United States with more than 103 million adults affected. While pharmacological treatments are effective, blood pressure (BP) remains uncontrolled in 50–60% of resistant hypertensive subjects. Using a custom-wired miniature electrode, we previously reported that deep peroneal nerve stimulation (DPNS) elicited acute cardiovascular depressor responses in anesthetized spontaneously hypertensive rats (SHRs). Here, we further study this effect by implementing a wireless system and exploring different stimulation parameters to achieve a maximum depressor response. Our results indicate that DPNS consistently induces a reduction in BP and suggests that renal sympathetic nerve activity (RSNA) is altered by this bioelectronic treatment. To test the acute effect of DPNS in awake animals, we developed a novel miniaturized wireless microchannel electrode (w-μCE), with a Z-shaped microchannel through which the target nerves slide and lock into the recording/stimulation chamber. Animals implanted with w-μCE and BP telemetry systems for 3 weeks showed an average BP of 150 ± 14 mmHg, which was reduced significantly by an active DPNS session to 135 ± 8 mmHg (p < 0.04), but not in sham-treated animals. The depressor response in animals with an active w-μCE was progressively returned to baseline levels 14 min later (164 ± 26 mmHg). This depressor response was confirmed in restrained fully awake animals that received DPNS for 10 days, where tail-cuff BP measurements showed that systolic BP in SHR lowered 10% at 1 h and 16% 2 h after the DPNS when compared to the post-implantation baseline. Together, these results support the use of DPN neuromodulation as a possible strategy to lower BP in drug-resistant hypertension.
Sarah F. McComish, Adina N. MacMahon Copas,
Frontiers in Neuroscience, Volume 16; https://doi.org/10.3389/fnins.2022.851058

Abstract:
Parkinson’s disease (PD) is the second most common neurodegenerative disease and affects approximately 2–3% of the population over the age of 65. PD is characterised by the loss of dopaminergic neurons from the substantia nigra, leading to debilitating motor symptoms including bradykinesia, tremor, rigidity, and postural instability. PD also results in a host of non-motor symptoms such as cognitive decline, sleep disturbances and depression. Although existing therapies can successfully manage some motor symptoms for several years, there is still no means to halt progression of this severely debilitating disorder. Animal models used to replicate aspects of PD have contributed greatly to our current understanding but do not fully replicate pathological mechanisms as they occur in patients. Because of this, there is now great interest in the use of human brain-based models to help further our understanding of disease processes. Human brain-based models include those derived from embryonic stem cells, patient-derived induced neurons, induced pluripotent stem cells and brain organoids, as well as post-mortem tissue. These models facilitate in vitro analysis of disease mechanisms and it is hoped they will help bridge the existing gap between bench and bedside. This review will discuss the various human brain-based models utilised in PD research today and highlight some of the key breakthroughs they have facilitated. Furthermore, the potential caveats associated with the use of human brain-based models will be detailed.
Hauke Basedau, Kuan-Po Peng, Arne May,
Frontiers in Neuroscience, Volume 16; https://doi.org/10.3389/fnins.2022.802239

Abstract:
The interest in exploring trigeminal pain processing has grown in recent years, mainly due to various pathologies (such as migraine) related to this system. However, research efforts have mainly focused on understanding molecular mechanisms or studying pathological states. On the contrary, non-invasive imaging studies are limited by either spatial or temporal resolution depending on the modality used. This can be overcome by using multimodal imaging techniques such as simultaneous functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). Although this technique has already been applied to neuroscientific research areas and consequently gained insights into diverse sensory systems and pathologies, only a few studies have applied EEG-fMRI in the field of pain processing and none in the trigeminal system. Focusing on trigeminal nociception, we used a trigeminal pain paradigm, which has been well-studied in either modality. For validation, we first acquired stand-alone measures with each imaging modality before fusing them in a simultaneous session. Furthermore, we introduced a new, yet simple, non-parametric correlation technique, which exploits trial-to-trial variance of both measurement techniques with Spearman’s correlations, to consolidate the results gained by the two modalities. This new technique does not presume a linear relationship and needs a few repetitions per subject. We also showed cross-validation by analyzing visual stimulations. Using these techniques, we showed that EEG power changes in the theta-band induced by trigeminal pain correlate with fMRI activation within the brainstem, whereas those of gamma-band oscillations correlate with BOLD signals in higher cortical areas.
Pan Zhang, Hanlin Wang, Weicong Ren, Huanhuan Guo, Jiayi Yang, Jiayu Tao, Zhijie Yang, Ying Li, Lijun Chen, Yajing Zhang, et al.
Frontiers in Neuroscience, Volume 16; https://doi.org/10.3389/fnins.2022.804576

Abstract:
It is critical to address the relationship between density label of Bangerter filters and expected visual acuity, and how filters modulate contrast sensitivity (CS) at different spatial frequency and external noise levels. In the current study, the monocular visual acuity and CS at ten spatial frequencies and three noise levels were measured in normal subjects wearing no filters, 0.8, 0.4, or 0.2 Bangerter filters. Compared with the baseline condition (no filter worn), Bangerter filters degraded both visual acuity and contrast sensitivity function (CSF) in zero-noise conditions, but the reduction of both visual functions did not correlate with each other at any filter level. In addition, the stronger the filter was, the worse both visual functions became. In contrast, when external noise was present, filters improved the contrast sensitivity at low frequencies but deteriorated it at intermediate and high spatial frequencies. The perceptual template model was used to reveal the corresponding mechanism accounted for filter-induced visual function changes. Although the internal process in visual system should not be affected by the filters, the measurement of parameters was biased. To be specific, (1) the internal additive noise was elevated at all frequencies; (2) the perceptual template was improved at low spatial frequencies but impaired at intermediate spatial frequencies; and (3) the changes in both factors were highly dependent on filter intensity. We conclude that Bangerter filters influence visual acuity and contrast sensitivity differently and that their effect on contrast sensitivity depends on spatial frequency and noise.
, Michael Streppel, Orlando Guntinas-Lichius, Nicole Fulgham-Scott, Johannes Vogt, Wolfram F. Neiss
Frontiers in Neuroscience, Volume 16; https://doi.org/10.3389/fnins.2022.895076

Abstract:
Purpose: Nimodipine and FK506 (Tacrolimus) are drugs that have been reported to accelerate peripheral nerve regeneration. We therefore tested these substances aiming to improve the final functional outcome of motoric reinnervation after facial nerve injury.Methods: In 18 female rats, the transected facial nerve was repaired by an artificial nerve conduit. The rats were then treated with either placebo, nimodipine, or FK506, for 56 days. Facial motoneurons were pre-operatively double-labeled by Fluoro-Gold and again 56 days post-operation by Fast-Blue to measure the cytological accuracy of reinnervation. The whisking motion of the vibrissae was analyzed to assess the quality of functional recovery.Results: On the non-operated side, 93–97% of those facial nerve motoneurons innervating the vibrissae were double-labeled. On the operated side, double-labeling only amounted to 38% (placebo), 40% (nimodipine), and 39% (FK506), indicating severe misdirection of reinnervation. Regardless of post-operative drug or placebo therapy, the whisking frequency reached 83–100% of the normal value (6.0 Hz), but whisking amplitude was reduced to 33–48% while whisking velocity reached 39–66% of the normal values. Compared to placebo, statistically neither nimodipine nor FK506 improved accuracy of reinnervation and function recovery.Conclusion: Despite previous, positive data on the speed and quantity of axonal regeneration, nimodipine and FK506 do not improve the final functional outcome of motoric reinnervation in rats.
Pan Zhang, Yeshuo Guo, Yuxin Qiao, Nan Yan, Yajing Zhang, Weicong Ren, Shilei Zhang,
Frontiers in Neuroscience, Volume 16; https://doi.org/10.3389/fnins.2022.873671

Abstract:
A reduction in visual performance is among the serious consequences of acute alcohol intake. Contrast sensitivity (CS) is a fundamental feature of visual function. Here, we investigated the negative effect of a moderate dose of alcohol on CS across a wide range of spatial frequencies and with multiple levels of external noise and clarified the corresponding mechanisms in the context of a perceptual template model (PTM). To avoid the effect of alcohol washout, a quick contrast sensitivity function (qCSF) method was used to assess the visual performance of subjects before and 30 min after a moderate dose of alcohol intake. We found that (1) CS was significantly disrupted by acute alcohol intake; (2) alcohol-induced CS loss was dependent on spatial frequency and external noise; and (3) increased internal additive noise and an impaired perceptual template accounted for alcohol-induced CS loss. These results help us better understand the negative effect of alcohol consumption and provide guidance for driver safety studies.
Yousheng Xiao, Hongchang Chen, Jiajia Liao, Qinxin Zhang, Honghu He, Jiang Lei, Jinjun Huang, Qiang Ouyang, Yuefei Shen,
Frontiers in Neuroscience, Volume 16; https://doi.org/10.3389/fnins.2022.893713

Abstract:
Parkinson’s disease (PD) is a progressive neurodegenerative disease. It has been reported that circular RNAs (circRNAs) play important roles in several neurological diseases. However, the role and regulatory networks of circRNAs in PD are still largely unclear. In this study, we first compared the global expression level of circRNAs from patients with PD and controls using microarray, then the candidate circRNAs were validated in another PD cohort. The possible functions of these candidate circRNAs were analyzed using Gene Ontology (GO) analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and the regulatory networks of these candidate circRNAs were constructed through circRNA–miRNA–mRNA regulatory networks, protein–protein interaction (PPI) networks, and transcription factor-circRNA networks. The results indicated that hsa_circRNA_101275, hsa_circRNA_103730, and hsa_circRNA_038416 were significantly more highly expressed in patients with PD, while hsa_circRNA_102850 was lower expressed in patients with PD when compared with controls. A circRNA panel combining the four differentially expressed circRNA showed a high diagnostic ability to distinguish patients with PD from controls (AUC = 0.938). Furthermore, GO and KEGG analysis showed these candidate circRNAs were enriched in PI3K–Akt and MAPK signaling pathways. We established circRNA–miRNA–mRNA regulatory networks and identified 10 hub genes (ESR1, PTEN, SHC1, IGF1R, SMAD2, KRAS, MDM2, HIF1A, BMP4, and ACVR2B) were closely related to PD by using PPI network analysis. Besides, these circRNAs were predicted to be regulated through tyrosine hydroxylase (TH)-relevant transcription factors such as GATA2 and GATA3. In conclusion, our results suggest that the circRNA panel and the established circRNA–miRNA–mRNA regulation networks might provide potential novel biomarkers and therapeutic targets for PD.
Weixia Zhang, Hongyang Wei, Xiaowen Chen, Yuyang Hou, Yujie Zhang,
Frontiers in Neuroscience, Volume 16; https://doi.org/10.3389/fnins.2022.858888

Abstract:
Each great architecture tells a story to make its space meaningful. What the stadium tells matters how the individual interacts with it. The potent influence of narrative in shaping our cognitive processing has been revealed and widely used. This influence, however, has not been the focus of researchers in stadium operations. The present study aimed at investigating the influence of the stadium narrative on approach-avoidance responses and the corresponding neural correlates. Participants were presented with a sequence of pictures expressing a story congruent or incongruent with the general profile of the stadium, and were required to make an enter or exit response. Results showed larger amplitudes of N400 for incongruent trials than congruent trials at the end of the narrative, indicating the feasibility of continuity editing procedure for the study of narratives. Moreover, larger amplitudes of LPP were observed in response to the stadium preceded by congruent trials than incongruent trials. This effect was more pronounced in the left than right frontal sites. The LPP suggested that a congruent narrative imparted the stadium approaching affective features, and induced approaching responses, which was consistent with the behavioral and correlational results. Our findings suggested that changes in narrative were sufficient to shape the approach-avoidance responses and the underlying neural correlates. Implications for stadium management and buildings are provided.
Jing-Ya Ren, Ming Zhu, Guanghai Wang, Yiding Gui, Fan Jiang, Su-Zhen Dong
Frontiers in Neuroscience, Volume 16; https://doi.org/10.3389/fnins.2022.886083

Abstract:
Objective: The purpose of this study is to establish a reference of intracranial structure volumes in normal fetuses ranging from 19 to 37 weeks' gestation (mean 27 weeks).Materials and Methods: A retrospective analysis of 188 MRI examinations (1.5 T) of fetuses with a normal brain appearance (19–37 gestational weeks) from January 2018 to December 2021 was included in this study. Three dimensional (3-D) volumetric parameters from slice-to-volume reconstructed (SVR) images, such as total brain volume (TBV), cortical gray matter volume (GMV), subcortical brain tissue volume (SBV), intracranial cavity volume (ICV), lateral ventricles volume (VV), cerebellum volume (CBV), brainstem volume (BM), and extra-cerebrospinal fluid volume (e-CSFV), were quantified by manual segmentation from two experts. The mean, SD, minimum, maximum, median, and 25th and 75th quartiles for intracranial structures volume were calculated per gestational week. A linear regression analysis was used to determine the gestational weekly age-related change adjusted for sex. A t-test was used to compare the mean TBV and ICV values to previously reported values at each gestational week. The formulas to calculate intracranial structures volume derived from our data were created using a regression model. In addition, we compared the predicted mean TBV values derived by our formula with the expected mean TBV predicted by the previously reported Jarvis' formula at each time point. For intracranial volumes, the intraclass correlation coefficient (ICC) was calculated to convey association within and between observers.Results: The intracranial volume data are shown in graphs and tabular summaries. The male fetuses had significantly larger VV compared with female fetuses (p = 0.01). Measured mean ICV values at 19 weeks are significantly different from those published in the literature (p < 0.05). Means were compared with the expected TBV generated by the previously reported formula, showing statistically differences at 22, 26, 29, and 30 weeks' gestational age (GA) (all p < 0.05). A comparison between our data-derived formula and the previously reported formula for TBV showed very similar values at every GA. The predicted TBV means derived from the previously reported formula were all within the 95% confidence interval (CI) of the predicted means of this study. Intra- and inter-observer agreement was high, with an intraclass correlation coefficient larger than 0.98.Conclusion: We have shown that the intracranial structural volume of the fetal brain can be reliably quantified using 3-D volumetric MRI with a high degree of reproducibility and reinforces the existing data with more robust data in the earlier second and third stages of pregnancy.
Qin Tian, Ling Wang, Yu Zhang, Ke Fan, Meng Liang, , Wen Qin, Hao Ding
Frontiers in Neuroscience, Volume 16; https://doi.org/10.3389/fnins.2022.885770

Abstract:
Purpose: The aim of this study was to investigate the brain gray matter volume (GMV) and spontaneous functional connectivity (FC) changes in patients with chronic Leber's hereditary optic neuropathy (LHON), and their relations with clinical measures.Methods: A total of 32 patients with chronic LHON and matched sighted healthy controls (HC) underwent neuro-ophthalmologic examinations and multimodel magnetic resonance imaging (MRI) scans. Voxel-based morphometry (VBM) was used to detect the GMV differences between the LHON and HC. Furthermore, resting-state FC analysis using the VBM-identified clusters as seeds was carried out to detect potential functional reorganization in the LHON. Finally, the associations between the neuroimaging and clinical measures were performed.Results: The average peripapillary retinal nerve fiber layer (RNFL) thickness of the chronic LHON was significantly thinner (T = −16.421, p < 0.001), and the mean defect of the visual field was significantly higher (T = 11.28, p < 0.001) than the HC. VBM analysis demonstrated a significantly lower GMV of bilateral calcarine gyri (CGs) in the LHON than in the HC (p < 0.05). Moreover, in comparison with the HC, the LHON had significantly lower FC between the centroid of the identified left CG and ipsilateral superior occipital gyrus (SOG) and higher FC between this cluster and the ipsilateral posterior cingulate gyrus (p < 0.05, corrected). Finally, the GMV of the left CG was negatively correlated with the LHON duration (r = −0.535, p = 0.002), and the FC between the left CG and the ipsilateral posterior cingulate gyrus of the LHON was negatively correlated with the average peripapillary RNFL thickness (r = −0.522, p = 0.003).Conclusion: The atrophied primary visual cortex of the chronic LHON may be caused by transneuronal degeneration following the retinal damage. Moreover, our findings suggest that the functional organization of the atrophied primary visual cortex has been reshaped in the chronic LHON.
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