A Narrative Review on the Clinical Relevance of Imaging the Circumventricular Brain Organs and Performing Their Anatomical and Histopathological Examination in Acute and Postacute COVID-19.

ABSTRACT: Autopsy followed by histopathological examination is foundational in clinical and forensic medicine for discovering and understanding pathological changes in disease, their underlying processes, and cause of death. Imaging technology has become increasingly important for advancing clinical research and practice, given its noninvasive, in vivo and ex vivo applicability. Medical and forensic autopsy can benefit greatly from advances in imaging technology that lead toward minimally invasive, whole-brain virtual autopsy. Brain autopsy followed by histopathological examination is still the hallmark for understanding disease and a fundamental modus operandi in forensic pathology and forensic medicine, despite the fact that its practice has become progressively less frequent in medical settings. This situation is especially relevant with respect to new diseases such as COVID-19 caused by the SARS-CoV-2 virus, for which our neuroanatomical knowledge is sparse. In this narrative review, we show that ad hoc clinical autopsies and histopathological analyses combined with neuroimaging of the principal circumventricular organs are critical to gaining insight into the reconstruction of the pathophysiological mechanisms and the explanation of cause of death (ie, atrium mortis) related to the cardiovascular effects of SARS-CoV-2 infection in forensic and clinical medicine.

Investigating the structural network underlying brain-immune interactions using combined histopathology and neuroimaging: a critical review for its relevance in acute and long COVID-19.

Current views on immunity support the idea that immunity extends beyond defense functions and is tightly intertwined with several other fields of biology such as virology, microbiology, physiology and ecology. It is also critical for our understanding of autoimmunity and cancer, two topics of great biological relevance and for critical public health considerations such as disease prevention and treatment. Central to this review, the immune system is known to interact intimately with the nervous system and has been recently hypothesized to be involved not only in autonomic and limbic bio-behaviors but also in cognitive function. Herein we review the structural architecture of the brain network involved in immune response. Furthermore, we elaborate upon the implications of inflammatory processes affecting brain-immune interactions as reported recently in pathological conditions due to SARS-Cov-2 virus infection, namely in acute and post-acute COVID-19. Moreover, we discuss how current neuroimaging techniques combined with ad hoc clinical autopsies and histopathological analyses could critically affect the validity of clinical translation in studies of human brain-immune interactions using neuroimaging. Advances in our understanding of brain-immune interactions are expected to translate into novel therapeutic avenues in a vast array of domains including cancer, autoimmune diseases or viral infections such as in acute and post-acute or Long COVID-19.

Electrochemical Detection of Bisphenol A Based on Gold Nanoparticles/Multi-Walled Carbon Nanotubes: Applications on Glassy Carbon and Screen Printed Electrodes.

Bisphenol A (BPA) has been classified as an endocrine-disrupting substance that may cause adverse effects on human health and the environment. The development of simple and sensitive electrochemical biosensors is crucial for the rapid and effective quantitative determination of BPA. This work presents a study on electrochemical sensors utilizing gold nanoparticle-modified multi-walled carbon nanotubes (CNT/AuNPs). Glassy carbon electrodes (GCEs) and screen-printed electrodes (SPEs) were conveniently modified and used for BPA detection. AuNPs were electrodeposited onto the CNT-modified electrodes using the galvanostatic method. The electrodes were properly modified and characterized by using Raman spectroscopy, cyclic voltammetry (CV), and electrochemical impedance analysis (EIS). The electrochemical response of the sensors was studied using differential pulse voltammetry (DPV) and constant potential amperometry (CPA) for modified GCE and SPE electrodes, respectively, and the main analytical parameters were studied and optimized. Problems encountered with the use of GCEs, such as sensor degradation and high limit of detection (LOD), were overcome by using modified SPEs and a flow injection device for the measurements. Under this approach, an LOD as low as 5 nM (S/N = 3) was achieved and presented a linear range up to 20 µM. Finally, our investigation addressed interference, reproducibility, and reusability aspects, successfully identifying BPA in both spiked and authentic samples, including commercial and tap waters. These findings underscore the practical applicability of our method for accurate BPA detection in real-world scenarios. Notably, the integration of SPEs and a flow injection device facilitated simplified automation, offering an exceptionally efficient and reliable solution for precise BPA detection in water analysis laboratories.

Empathy Modulates the Activity of the Sensorimotor Mirror Neuron System during Pain Observation.

AIM: The aim of this study is to analyze the brain activity patterns during the observation of painful expressions and to establish the relationship between this activity and the scores obtained on the Interpersonal Reactivity Index (IRI). METHODS: The study included twenty healthy, right-handed subjects (10 women). We conducted a task-based and resting-state functional magnetic resonance imaging (fMRI) study. The task involved observing pictures displaying painful expressions. We performed a region of interest (ROI) analysis focusing on the core regions of the sensorimotor mirror neuron system (MNS). Resting-state fMRI was utilized to assess the functional connectivity of the sensorimotor MNS regions with the rest of the cortex using a seed-to-voxel approach. Additionally, we conducted a regression analysis to examine the relationship between brain activity and scores from the IRI subtests. RESULTS: Observing painful expressions led to increased activity in specific regions of the frontal, temporal, and parietal lobes. The largest cluster of activation was observed in the left inferior parietal lobule (IPL). However, the ROI analysis did not reveal any significant activity in the remaining core regions of the sensorimotor MNS. The regression analysis demonstrated a positive correlation between brain activity during the observation of pain and the "empathic concern" subtest scores of the IRI in both the cingulate gyri and bilateral IPL. Finally, we identified a positive relationship between the "empathic concern" subtest of the IRI and the functional connectivity (FC) of bilateral IPLs with the bilateral prefrontal cortex and the right IFG. CONCLUSION: Observing expressions of pain triggers activation in the sensorimotor MNS, and this activation is influenced by the individual's level of empathy.

Medial temporal lobe contributions to resting-state networks.

The medial temporal lobe (MTL) is a set of interconnected brain regions that have been shown to play a central role in behavior as well as in neurological disease. Recent studies using resting-state functional magnetic resonance imaging (rsfMRI) have attempted to understand the MTL in terms of its functional connectivity with the rest of the brain. However, the exact characterization of the whole-brain networks that co-activate with the MTL as well as how the various sub-regions of the MTL are associated with these networks remains poorly understood. Here, we attempted to advance these issues by exploiting the high spatial resolution 7T rsfMRI dataset from the Human Connectome Project with a data-driven analysis approach that relied on independent component analysis (ICA) restricted to the MTL. We found that four different well-known resting-state networks co-activated with a unique configuration of MTL subcomponents. Specifically, we found that different sections of the parahippocampal cortex were involved in the default mode, visual and dorsal attention networks; sections of the hippocampus in the somatomotor and default mode networks; and the lateral entorhinal cortex in the dorsal attention network. We replicated this set of results in a validation sample. These results provide new insight into how the MTL and its subcomponents contribute to known resting-state networks. The participation of the MTL in an expanded range of resting-state networks is in line with recent proposals on MTL function.

Resting State Functional Connectivity Associated With Sahaja Yoga Meditation.

Neuroscience research has shown that meditation practices have effects on brain structure and function. However, few studies have combined information on the effects on structure and function in the same sample. Long-term daily meditation practice produces repeated activity of specific brain networks over years of practice, which may induce lasting structural and functional connectivity (FC) changes within relevant circuits. The aim of our study was therefore to identify differences in FC during the resting state between 23 Sahaja Yoga Meditation experts and 23 healthy participants without meditation experience. Seed-based FC analysis was performed departing from voxels that had shown structural differences between these same participants. The contrast of connectivity maps yielded that meditators showed increased FC between the left ventrolateral prefrontal cortex and the right dorsolateral prefrontal cortex but reduced FC between the left insula and the bilateral mid-cingulate as well as between the right angular gyrus and the bilateral precuneus/cuneus cortices. It thus appears that long-term meditation practice increases direct FC between ventral and dorsal frontal regions within brain networks related to attention and cognitive control and decreases FC between regions of these networks and areas of the default mode network.

N-Acetylaspartyl-Glutamate Metabolism in the Cingulated Cortices as a Biomarker of the Etiology in ASD: A 1H-MRS Model.

As brain functional resonance magnetic studies show an aberrant trajectory of neurodevelopment, it is reasonable to predict that the degree of neurochemical abnormalities indexed by magnetic resonance spectroscopy (1H-MRS) might also change according to the developmental stages and brain regions in autism spectrum disorders (ASDs). Since specific N-Acetyl-aspartate (NAA) changes in children's metabolism have been found in the anterior cingulate cortex (ACC) but not in the posterior cingulate cortex (PCC), we analyzed whether the metabolites of ASD youths change between the cingulate cortices using 1H-MRS. l-glutamate (Glu) and l-Acetyl-aspartate (NAA) are products from the N-Acetyl-aspartyl-glutamate (NAAG) metabolism in a reaction that requires the participation of neurons, oligodendrocytes, and astrocytes. This altered tri-cellular metabolism has been described in several neurological diseases, but not in ASD. Compared to the typical development (TD) group, the ASD group had an abnormal pattern of metabolites in the ACC, with a significant increase of glutamate (12.10 ± 3.92 mM; p = 0.02); additionally, N-Acetyl-aspartyl-glutamate significantly decreased (0.41 ± 0.27 mM; p = 0.02) within ASD metabolism abnormalities in the ACC, which may allow the development of new therapeutic possibilities.

Music Style Not Only Modulates the Auditory Cortex, but Also Motor Related Areas.

The neuroscience of music has recently attracted significant attention, but the effect of music style on the activation of auditory-motor regions has not been explored. The aim of the present study is to analyze the differences in brain activity during passive listening to non-vocal excerpts of four different music genres (classical, reggaeton, electronic and folk). A functional magnetic resonance imaging (fMRI) experiment was performed. Twenty-eight participants with no musical training were included in the study. They had to passively listen to music excerpts of the above genres during fMRI acquisition. Imaging analysis was performed at the whole-brain-level and in auditory-motor regions of interest (ROIs). Furthermore, the musical competence of each participant was measured and its relationship with brain activity in the studied ROIs was analyzed. The whole brain analysis showed higher brain activity during reggaeton listening than the other music genres in auditory-related areas. The ROI-analysis showed that reggaeton led to higher activity not only in auditory related areas, but also in some motor related areas, mainly when it was compared with classical music. A positive relationship between the melodic-Music Ear Test (MET) score and brain activity during reggaeton listening was identified in some auditory and motor related areas. The findings revealed that listening to different music styles in musically inexperienced subjects elicits different brain activity in auditory and motor related areas. Reggaeton was, among the studied music genres, the one that evoked the highest activity in the auditory-motor network. These findings are discussed in connection with acoustic analyses of the musical stimuli.

Diffuse optical tomography to measure functional changes during motor tasks: a motor imagery study.

The present work shows the spatial reliability of the diffuse optical tomography (DOT) system in a group of healthy subjects during a motor imagery task. Prior to imagery task performance, the subjects executed a motor task based on the finger to thumb opposition for motor training, and to corroborate the DOT spatial localization during the motor execution. DOT technology and data treatment allows us to distinguish oxy- and deoxyhemoglobin at the cerebral gyri level unlike the cerebral activations provided by fMRI series that were processed using different approaches. Here we show the DOT reliability showing functional activations at the cerebral gyri level during motor execution and motor imagery, which provide subtler cerebral activations than the motor execution. These results will allow the use of the DOT system as a monitoring device in a brain computer interface.

Larger whole brain grey matter associated with long-term Sahaja Yoga Meditation: A detailed area by area comparison.

OBJECTIVES: Our previous study showed that long-term practitioners of Sahaja Yoga Meditation (SYM) had around 7% larger grey matter volume (GMV) in the whole brain compared with healthy controls; however, when testing individual regions, only 5 small brain areas were statistically different between groups. Under the hypothesis that those results were statistically conservative, with the same dataset, we investigated in more detail the regional differences in GMV associated with the practice of SYM, with a different statistical approach. DESIGN: Twenty-three experienced practitioners of SYM and 23 healthy non-meditators matched on age, sex and education level, were scanned using structural magnetic resonance imaging (MRI). Their GMV were extracted and compared using Voxel-Based Morphometry (VBM). Using a novel ad-hoc general linear model, statistical comparisons were made to observe if the GMV differences between meditators and controls were statistically significant. RESULTS: In the 16 lobe area subdivisions, GMV was statistically significantly different in 4 out of 16 areas: in right hemispheric temporal and frontal lobes, left frontal lobe and brainstem. In the 116 AAL area subdivisions, GMV difference was statistically significant in 11 areas. The GMV differences were statistically more significant in right hemispheric brain areas. CONCLUSIONS: The study shows that long-term practice of SYM is associated with larger GMV overall, and with significant differences mainly in temporal and frontal areas of the right hemisphere and the brainstem. These neuroplastic changes may reflect emotional and attentional control mechanisms developed with SYM. On the other hand, our statistical ad-hoc method shows that there were more brain areas with statistical significance compared to the traditional methodology which we think is susceptible to conservative Type II errors.

Visual inputs decrease brain activity in frontal areas during silent lipreading.

AIM: The aim of the present work is to analyze the modulation of the brain activity within the areas involved in lipreading when an additional visual stimulus is included. METHODS: The experiment consisted of two fMRI runs (lipreading_only and lipreading+picture) where two conditions were considered in each one (oral speech sentences condition [OSS] and oral speech syllables condition [OSSY]). RESULTS: During lipreading-only, higher activity in the left middle temporal gyrus (MTG) was identified for OSS than OSSY; during lipreading+picture, apart from the left MTG, higher activity was also present in the supplementary motor area (SMA), the left precentral gyrus (PreCG) and the left inferior frontal gyrus (IFG). The comparison between these two runs revealed higher activity for lipreading-only in the SMA and the left IFG. CONCLUSION: The presence of a visual reference during a lipreading task leads to a decrease in activity in frontal areas.

Developmental grey matter changes in superior parietal cortex accompany improved transitive reasoning.

The neural basis of developmental changes in transitive reasoning in parietal regions was examined, using voxel-based morphometry. Young adolescents and adults performed a transitive reasoning task, subsequent to undergoing anatomical magnetic resonance imaging (MRI) brain scans. Behaviorally, adults reasoned more accurately than did the young adolescents. Neural results showed (i) less grey matter density in superior parietal cortex in the adults than in the young adolescents, possibly due to a developmental period of synaptic pruning; (ii) improved performance in the reasoning task was negatively correlated with grey matter density in superior parietal cortex in the adolescents, but not in the adult group; and (iii) the latter results were driven by the more difficult trials, requiring greater spatial manipulation. Taken together, the results support the idea that during development, regions in superior parietal cortex are fine-tuned, to support more robust spatial manipulation, resulting in greater accuracy and efficiency in transitive reasoning.

The relationship between amplitude of low frequency fluctuations and gray matter volume of the mirror neuron system: Differences between low disability multiple sclerosis patients and healthy controls.

The study of the relationship between function and structure of the brain could be particularly interesting in neurodegenerative diseases like multiple sclerosis (MS). The aim of the present work is to identify differences of the amplitude of low frequency fluctuations (ALFF) in the mirror neuron system (MNS) between MS patients and healthy controls and to study the relationship between ALFF and the gray matter volume (GMV) of the regions that belong to the MNS. Relapsing-remitting MS patients with minor disability were compared to healthy controls (HC) using resting-state functional magnetic resonance imaging (fMRI), anatomic T1 weighted images and diffusion tensor imaging (DTI). Region of interest (ROI) analyses was performed in the MNS regions. A decrease of ALFF in MS patients was observed in the left inferior frontal gyrus (IFG). Furthermore, a correlation between ALFF in the IFG and the GMV of the left inferior parietal lobule (IPL) was identified. This relationship was different for MS patients than for HC, which may be associated with changes in diffusivity measures which were impaired in MS patients. MS patients with low disability may show ALFF differences in the MNS without clinical correspondence. This functional difference may be associated with cortical and subcortical changes related to the disease.

Gray Matter and Functional Connectivity in Anterior Cingulate Cortex are Associated with the State of Mental Silence During Sahaja Yoga Meditation.

Some meditation techniques teach the practitioner to achieve the state of mental silence. The aim of this study was to investigate brain regions that are associated with their volume and functional connectivity (FC) with the depth of mental silence in long-term practitioners of Sahaja Yoga Meditation. Twenty-three long-term practitioners of this meditation were scanned using Magnetic Resonance Imaging. In order to identify the neural correlates of the depth of mental silence, we tested which gray matter volumes (GMV) were correlated with the depth of mental silence and which regions these areas were functionally connected to under a meditation condition. GMV in medial prefrontal cortex including rostral anterior cingulate cortex were positively correlated with the subjective perception of the depth of mental silence inside the scanner. Furthermore, there was significantly increased FC between this area and bilateral anterior insula/putamen during a meditation-state specifically, while decreased connectivity with the right thalamus/parahippocampal gyrus was present during the meditation-state and the resting-state. The capacity of long-term meditators to establish a durable state of mental silence inside an MRI scanner was associated with larger gray matter volume in a medial frontal region that is crucial for top-down cognitive, emotion and attention control. This is furthermore corroborated by increased FC of this region during the meditation-state with bilateral anterior insula/putamen, which are important for interoception, emotion, and attention regulation. The findings hence suggest that the depth of mental silence is associated with medial fronto-insular-striatal networks that are crucial for top-down attention and emotional control.

Comparing diffuse optical tomography and functional magnetic resonance imaging signals during a cognitive task: pilot study.

Diffuse optical tomography (DOT) measures concentration changes in both oxy- and deoxyhemoglobin providing three-dimensional images of local brain activations. A pilot study, which compares both DOT and functional magnetic resonance imaging (fMRI) volumes through t-maps given by canonical statistical parametric mapping (SPM) processing for both data modalities, is presented. The DOT series were processed using a method that is based on a Bayesian filter application on raw DOT data to remove physiological changes and minimum description length application index to select a number of singular values, which reduce the data dimensionality during image reconstruction and adaptation of DOT volume series to normalized standard space. Therefore, statistical analysis is performed with canonical SPM software in the same way as fMRI analysis is done, accepting DOT volumes as if they were fMRI volumes. The results show the reproducibility and ruggedness of the method to process DOT series on group analysis using cognitive paradigms on the prefrontal cortex. Difficulties such as the fact that scalp-brain distances vary between subjects or cerebral activations are difficult to reproduce due to strategies used by the subjects to solve arithmetic problems are considered. T-images given by fMRI and DOT volume series analyzed in SPM show that at the functional level, both DOT and fMRI measures detect the same areas, although DOT provides complementary information to fMRI signals about cerebral activity.

The Mirror Neuron System in Relapsing Remitting Multiple Sclerosis Patients with Low Disability.

To study the visuospatial/visuoperceptive function using a mirror neuron system (MNS) based approach in multiple sclerosis (MS) patients and a healthy control group. Two task-based fMRIs (an execution task and an observation task) and one resting-fMRI were performed in a group of MS patients (n = 24) and a group of healthy controls (n = 15). The execution and observation tasks consisted of the performance or observation of the index-thumb opposition task. Statistical parametric mapping approaches were used to identify differences in the brain activity and functional connectivity (FC) of the MNS between MS patients and healthy controls. Furthermore, visuospatial and visuoperceptive evaluation was performed by a neuropsychologist on all the participants. No global differences between groups were identified when the activity during both the execution and the observation conditions was tested. Nevertheless, differences in FC maps were identified: healthy controls showed higher connectivity between the MNS regions (between the inferior parietal lobule and the inferior frontal gyrus bilaterally) than MS patients. The absence of differences between the studied groups may be the consequence of the selection of a cohort of MS patients with low disability and with no recent relapse. However, the presence of a decrease in functional connectivity within the MNS in MS patients could indicate the presence of subclinical disability in MNS functioning, not measurable by neuropsychological tests.

The mirror neuron system also rests.

The mirror neuron system (MNS) is a brain network that has been associated with the understanding of the actions performed by others. The main areas of the brain that are considered as belonging to the MNS are the rostral part of the inferior parietal lobe (IPL) and the inferior frontal gyrus (IFG). Many studies have tried to focus on the relationship between the regions belonging to the MNS, but a little consideration has been given to the study of the MNS in resting conditions. In the present experiment, the MNS has been studied by two fMRI modalities (task-based fMRI and resting-fMRI) and three analytical procedures [task-block comparison, functional connectivity (FC), and independent component analysis (ICA)]. The task-fMRI with block design showed a mirror activity located in the rostral IPL. The coordinates of this local maximum voxel were defined as a region of interest (ROI) for an FC analysis of the resting-fMRI. This analysis revealed the existence of a functional connectivity within regions forming the core of MNS network and also with other regions with mirror properties. Finally, resting-state fMRI ICA showed the same functional network, although it was more restricted to the core MNS regions. To the best of our knowledge, this is the first study that approaches the MNS using the resting-state fMRI analysis using independent component analysis and functional connectivity at the same time.

Subarachnoid hemorrhage and visuospatial and visuoperceptive impairment: disruption of the mirror neuron system.

Nearly 20 % of patients who suffer a subarachnoid hemorrhage (SAH) still display cognitive impairment even a year after follow-up. Visuospatial and visuoperceptive domains may be impaired in this cognitive impairment and may not have been fully studied in these patients. Furthermore, these cognitively impaired domains have been associated with activity in the so-called mirror neuron system (MNS). The aim of the study is to analyze the pattern of brain activity with an MNS task-based functional magnetic resonance imaging (fMRI) study in SAH patients. A complete neuropsychological assessment and fMRI study (with observation and execution conditions) were performed in patients with a history of SAH registered in the database of the Hospital Universitario de Canarias and a healthy control group. The patients had to meet all the following inclusion criteria for the study (less than 50 years old; SAH with a Fisher score 1-3; no vasospasm or ischemia; minimum follow-up of one year). Twelve SAH patients were studied. Three of which displayed visuospatial/visuoperceptive impairment. fMRI study showed the presence of higher activity in MNS regions in these patients than in patients with normal visuospatial/visuoperceptive functions. Furthermore, there was a negative correlation between the test scores and brain activity in premotor regions of the studied patients. SAH patients with visuospatial/visuoperceptive impairment have greater activity in the MNS regions. This finding may be associated with a subcortical dysfunction, leading to a disruption of neural activity and less efficient behavior of this brain network.

Increased Grey Matter Associated with Long-Term Sahaja Yoga Meditation: A Voxel-Based Morphometry Study.

OBJECTIVES: To investigate regional differences in grey matter volume associated with the practice of Sahaja Yoga Meditation. DESIGN: Twenty three experienced practitioners of Sahaja Yoga Meditation and twenty three non-meditators matched on age, gender and education level, were scanned using structural Magnetic Resonance Imaging and their grey matter volume were compared using Voxel-Based Morphometry. RESULTS: Grey matter volume was larger in meditators relative to non-meditators across the whole brain. In addition, grey matter volume was larger in several predominantly right hemispheric regions: in insula, ventromedial orbitofrontal cortex, inferior temporal and parietal cortices as well as in left ventrolateral prefrontal cortex and left insula. No areas with larger grey matter volume were found in non-meditators relative to meditators. CONCLUSIONS: The study shows that long-term practice of Sahaja Yoga Meditation is associated with larger grey matter volume overall, and with regional enlargement in several right hemispheric cortical and subcortical brain regions that are associated with sustained attention, self-control, compassion and interoceptive perception. The increased grey matter volume in these attention and self-control mediating regions suggests use-dependent enlargement with regular practice of this meditation.

Application of Prussian Blue electrodes for amperometric detection of free chlorine in water samples using Flow Injection Analysis.

The performance for free chlorine detection of surfactant-modified Prussian Blue screen printed carbon electrodes (SPCEs/PB-BZT) have been assessed by cyclic voltammetry and constant potential amperometry. The characterization of SPCEs/PB-BZT by X-ray photoemission, Raman and infrared spectroscopies confirmed the correct electrodeposition of the surfactant-modified PB film. These electrodes were incorporated in a Flow Injection device and the optimal working conditions determined as a function of experimental variables such as detection potential, electrolyte concentration or flow-rate. The sensor presented a linear response in the range 0-3 ppm free chlorine, with a sensitivity of 16.2 µA ppm(-1) cm(-2). The limit of detection (LOD) (S/N=3.3) and the limit of quantification (S/N=10) amounted to 8.25 and 24.6 ppb, respectively, adequate for controlling tap and drinking waters. To demonstrate the feasibility of using this free chlorine sensor for real applications possible interferences such as nitrate, nitrite and sulfate ions were successfully tested and discarded. Real free chlorine analysis was carried out in spiked tap water samples and commercial bleaches.