Synergistic effect of photothermal and magnetic hyperthermia for in situ activation of Fenton reaction in tumor microenvironment for chemodynamic therapy.

Traditional cancer treatments are ineffective and cause severe adverse effects. Thus, the development of chemodynamic therapy (CDT) has the potential for in situ catalysis of endogenous molecules into highly toxic species, which would then effectively destroy cancer cells. However, the shortage of high-performance nanomaterials hinders the broad clinical application of this approach. In present study, an effective therapeutic platform was developed using a simple hydrothermal method for the in-situ activation of the Fenton reaction within the tumor microenvironment (TME) to generate substantial quantities of •OH and ultimately destroy cancer cells, which could be further synergistically increased by photothermal therapy (PHT) and magnetic hyperthermia (MHT) aided by FeMoO4 nanorods (NRs). The produced FeMoO4 NRs were used as MHT/PHT and Fenton catalysts. The photothermal conversion efficiency of the FeMoO4 NRs was 31.75 %. In vitro and \ experiments demonstrated that the synergistic combination of MHT/PHT/CDT notably improved anticancer efficacy. This work reveals the significant efficacy of CDT aided by both photothermal and magnetic hyperthermia and offers a feasible strategy for the use of iron-based nanoparticles in the field of biomedical applications.

Multi-Modal Synergistic 99mTc-TRODAT-1 SPECT and MRI for Evaluation of the Efficacy of Hyperbaric Oxygen Therapy in CO-Induced Delayed Parkinsonian and Non-Parkinsonian Syndromes.

Background: Delayed neuropsychiatric syndrome (DNS) is characterized by motor dysfunction after acute carbon monoxide (CO) poisoning. We examined the relationship between dopamine transporter (DAT) loss using kit-based Tc-99m-TRODAT-1 (DAT single-photon emission-computed tomography (SPECT) radioligand) and globus pallidus necrosis on MRI, DAT availability before and after hyperbaric oxygen therapy (HBOT), and feasibility of Tc-99m-TRODAT-1 as an index for parkinsonian syndrome in CO poisoning. Methods: Twenty-one CO-intoxicated patients (mean ± SD age, 38.6 ± 11.4; range, 20−68 years) with DNS underwent Tc-99m-TRODAT-1 SPECT and MRI before HBOT and follow-up Tc-99m-TRODAT-1 SPECT to assess DAT recovery. Neurological examinations for Parkinsonism were performed after development of DNS. Results: Over 70% (15/21) of DNS patients showed globus pallidus necrosis on MRI. Significantly lower bilateral striatal DAT availability was associated with globus pallidus necrosis (p < 0.005). Moreover, 68.4% (13/19) of DNS subjects with Parkinsonian syndrome had lower bilateral striatal DAT availability vs. non-parkinsonian subjects pre- or post-HBOT. The SURs for both striata increased by ~11% post-HBOT in the Parkinsonian group; however, the left striatum presented a significantly higher DAT recovery rate than the right (*** p < 0.005). Conclusions: Coupled Tc-99m TRODAT-1 SPECT and MRI could assist evaluation of Parkinsonism risk and indicate DAT availability after HBOT in CO-poisoned patients with DNS.

Common abnormal connectivity in first-episode and chronic schizophrenia in pre- and post-central regions: Implications for neuromodulation targeting.

Schizophrenia is a neurodevelopmental disorder manifesting differing impairments at early onset and chronic disease stages. Brain imaging research suggests a core pathological region in patients with first-episode schizophrenia is Broca's area. With disease progression, alterations in thalamic connectivity becomes more prevalent. Understanding the common circuitry underlying pathology in these two groups might highlight a critical common network and novel targets for treatment. In this study, 937 subject samples were collected including patients with first-episode schizophrenia and those with chronic schizophrenia. We used hypothesis-based voxel-level functional connectivity analyses to calculate functional connectivity using the left Broca's area and thalamus as regions of interest in those with first-episode and chronic schizophrenia, respectively. We show for the first time that in both patients with first-episode and chronic schizophrenia the greatest functional connectivity disruption ended in the pre- and postcentral regions. At the early-onset stage, the core brain region is abnormally connected to pre- and postcentral areas responsible for mouth movement, while in the chronic stage, it expanded to a wider range of sensorimotor areas. Our findings suggest that expanding the focus on the low-order sensory-motor systems beyond high-order cognitive impairments in schizophrenia may show potential for neuromodulation treatment, given the relative accessibility of these cortical regions and their functional and structural connections to the core region at different stages of illness.

Hippocampus- and thalamus-related fiber-specific white matter reductions in mild cognitive impairment.

Early diagnosis of mild cognitive impairment (MCI) fascinates screening high-risk Alzheimer's disease (AD). White matter is found to degenerate earlier than gray matter and functional connectivity during MCI. Although studies reveal white matter degenerates in the limbic system for MCI, how other white matter degenerates during MCI remains unclear. In our method, regions of interest with a high level of resting-state functional connectivity with hippocampus were selected as seeds to track fibers based on diffusion tensor imaging (DTI). In this way, hippocampus-temporal and thalamus-related fibers were selected, and each fiber's DTI parameters were extracted. Then, statistical analysis, machine learning classification, and Pearson's correlations with behavior scores were performed between MCI and normal control (NC) groups. Results show that: 1) the mean diffusivity of hippocampus-temporal and thalamus-related fibers are significantly higher in MCI and could be used to classify 2 groups effectively. 2) Compared with normal fibers, the degenerated fibers detected by the DTI indexes, especially for hippocampus-temporal fibers, have shown significantly higher correlations with cognitive scores. 3) Compared with the hippocampus-temporal fibers, thalamus-related fibers have shown significantly higher correlations with depression scores within MCI. Our results provide novel biomarkers for the early diagnoses of AD.

An extended Human Connectome Project multimodal parcellation atlas of the human cortex and subcortical areas.

A modified and extended version, HCPex, is provided of the surface-based Human Connectome Project-MultiModal Parcellation atlas of human cortical areas (HCP-MMP v1.0, Glasser et al. 2016). The original atlas with 360 cortical areas has been modified in HCPex for ease of use with volumetric neuroimaging software, such as SPM, FSL, and MRIcroGL. HCPex is also an extended version of the original atlas in which 66 subcortical areas (33 in each hemisphere) have been added, including the amygdala, thalamus, putamen, caudate nucleus, nucleus accumbens, globus pallidus, mammillary bodies, septal nuclei and nucleus basalis. HCPex makes available the excellent parcellation of cortical areas in HCP-MMP v1.0 to users of volumetric software, such as SPM and FSL, as well as adding some subcortical regions, and providing labelled coronal views of the human brain.

Cerebellar-limbic neurocircuit is the novel biosignature of physio-cognitive decline syndrome.

Both physical and cognitive deficits occur in the aging process. We operationally defined the phenomenon as physio-cognitive decline syndrome (PCDS) and aimed to decipher its corresponding neuroanatomy patterns and neurocircuit. High resolution 3T brain magnetic resonance imaging (MRI) images from a community-dwelling longitudinal aging cohort were analysed. PCDS was defined as weakness (handgrip strength) and/or slowness (gait speed) concomitant with impairment in any cognitive domain (defined by 1.5 standard deviation below age, sex-matched norms), but without dementia or disability. Among 1196 eligible ≥ 50-year-old (62±9 years, 47.6%men) subjects, 15.9% had PCDS. Compared to the other participants, individuals with PCDS had significantly lower gray-matter volume (GMV) in the bilateral amygdala and thalamus, right hippocampus, right temporo-occipital cortex, and left cerebellum VI and V regions. The regions of reduced GMV in people with PCDS were similar between the middle-aged and older adults; whereas larger clusters with more extensive GMV-depleted regions were observed in ≥65-year-olds with PCDS. Diffusion-weighted tractography showed disrupted hippocampus-amygdala-cerebellum connections in subjects with PCDS. The neuroanatomic characteristics revealed by this study provide evidence for pathophysiological processes associated with concomitant physio-cognitive decline in the elderly. This neurocircuit might constitute a target for future preventive interventions.

Functional, Anatomical, and Morphological Networks Highlight the Role of Basal Ganglia-Thalamus-Cortex Circuits in Schizophrenia.

Evidence from electrophysiological, functional, and structural research suggests that abnormal brain connectivity plays an important role in the pathophysiology of schizophrenia. However, most previous studies have focused on single modalities only, each of which is associated with its own limitations. Multimodal combinations can more effectively utilize various information, but previous multimodal research mostly focuses on extracting local features, rather than carrying out research based on network perspective. This study included 135 patients with schizophrenia and 148 sex- and age-matched healthy controls. Functional magnetic resonance imaging, diffusion tensor imaging, and structural magnetic resonance imaging data were used to construct the functional, anatomical, and morphological networks of each participant, respectively. These networks were used in combination with machine learning to identify more consistent biomarkers of brain connectivity and explore the relationships between different modalities. We found that although each modality had divergent connectivity biomarkers, the convergent pattern was that all were mostly located within the basal ganglia-thalamus-cortex circuit. Furthermore, using the biomarkers of these 3 modalities as a feature yielded the highest classification accuracy (91.75%, relative to a single modality), suggesting that the combination of multiple modalities could be effectively utilized to obtain complementary information regarding different mode networks; furthermore, this information could help distinguish patients. These findings provide direct evidence for the disconnection hypothesis of schizophrenia, suggesting that abnormalities in the basal ganglia-thalamus-cortex circuit can be used as a biomarker of schizophrenia.

Bench to bedside review: Possible role of vitamin D in autism spectrum disorder.

Autism spectrum disorder (ASD) is a group of dysfunctions in social interaction, communication, and behaviors. Studies have demonstrated that vitamin D deficiency during pregnancy and in individuals increased the risk of ASD. A genetic polymorphism study has pinpointed that genotype AA/A-allele of GC rs4588 in children is associated with ASD, which encodes the vitamin D binding protein. Translating the mentioned points into clinical practice, several clinical trials have demonstrated that vitamin D supplementation can improve the core symptoms in children with ASD. One paper also showed that possible prophylactic effect for the reoccurrence of ASD by vitamin D supplement during pregnancy and early childhood. Herein, this review aims to address the recent advances in this field and to clarify the possible role of vitamin D in ASD.

Gender difference in the theta/alpha ratio during the induction of peaceful audiovisual modalities.

Gender differences in emotional perception have been found in numerous psychological and psychophysiological studies. The conducting modalities in diverse characteristics of different sensory systems make it interesting to determine how cooperation and competition contribute to emotional experiences. We have previously estimated the bias from the match attributes of auditory and visual modalities and revealed specific brain activity frequency patterns related to a peaceful mood. In that multimodality experiment, we focused on how inner-quiet information is processed in the human brain, and found evidence of auditory domination from the theta-band activity. However, a simple quantitative description of these three frequency bands is lacking, and no studies have assessed the effects of peacefulness on the emotional state. Therefore, the aim of this study was to use magnetoencephalography to determine if gender differences exist (and when and where) in the frequency interactions underpinning the perception of peacefulness. This study provides evidence of auditory and visual domination in perceptual bias during multimodality processing of peaceful consciousness. The results of power ratio analyses suggest that the values of the theta/alpha ratio are associated with a modality as well as hemispheric asymmetries in the anterior-to-posterior direction, which shift from right to left with the auditory to visual stimulations in a peaceful mood. This means that the theta/alpha ratio might be useful for evaluating emotion. Moreover, the difference was found to be most pronounced for auditory domination and visual sensitivity in the female group.

Altered hypothalamic functional connectivity in cluster headache: a longitudinal resting-state functional MRI study.

BACKGROUND: Neuroimaging studies implicate hypothalamic dysfunction in the pathogenesis of cluster headache (CH). Disruptions in non-traditional pain processing areas, including the cerebellum and visual cortex, have also been reported in CH. It is unknown whether the hypothalamus interacts significantly with these areas, and whether any such interactions vary between the 'in-bout' and 'out-of-bout' periods in CH. This study aimed to investigate the resting-state functional connectivity (FC) of the hypothalamus of patients with CH. METHODS: Using 3-T functional MRI, we conducted a seed-based resting-state intrinsic FC analysis of the hypothalamus in 18 episodic CH patients during in-bout and out-of-bout periods, and in 19 healthy controls. Correlations between hypothalamic FC and clinical variables were also assessed. RESULTS: Compared to controls, CH patients showed hypothalamic FC changes with the medial frontal gyrus and occipital cuneus during in-bout and out-of-bout periods. Compared to out-of-bout scans, in-bout scans revealed decreased hypothalamic FC with the medial frontal gyrus, precuneus, and cerebellar areas (tonsil, declive and culmen). Additionally, the annual bout frequency correlated significantly with the hypothalamic FC in the cerebellar culmen (r=-0.576, p=0.02) and cerebellar declive (r=-0.522, p=0.038). CONCLUSIONS: Our findings suggest that in CH, FC differences between the hypothalamus and its regional distribution extends beyond traditional pain processing areas, primarily to the cerebellar, frontal and occipital areas. These changes may be important and associated with CH pathophysiology.

Disrupted thalamo-cortical connectivity in schizophrenia: a morphometric correlation analysis.

Increasing studies have implicated the thalamus in schizophrenia, supporting the view that this structure has an important role in this disorder. Given that extensive reciprocal connections exist between the thalamus and the cerebral cortex, it is believed that disruptions of the thalamo-cortical connections may underlie the multiplicity of schizophrenic symptoms. Therefore, assessing the relationship between the thalamus and the neocortex may provide new insights into the pathophysiology of schizophrenia. We analyzed magnetic resonance images from a sample of 101 schizophrenic patients and 101 healthy controls. By assessing the correlation between the thalamic volume and cortical thickness at each vertex on the cortical surface, a thalamo-cortical network was obtained for each group. We compared the patterns of thalamo-cortical connectivity between the two groups. Compared with healthy controls, less distributed cortical regions were identified in the thalamo-cortical network in patients with schizophrenia. Vertex-wise comparison revealed decreased thalamo-cortical connectivity in bilateral inferior frontal gyrus, the left superior temporal gyrus and the right parieto-occipital region in schizophrenia. The observed disruptions in thalamo-cortical connectivity might be the substrate underlying the wide range of schizophrenic symptoms and provide further evidence to support the notion of schizophrenia as a disorder of brain dysconnectivity.

Expertise modulates the perception of pain in others.

Perceiving the pain of others activates a large part of the pain matrix in the observer [1]. Because this shared neural representation can lead to empathy or personal distress [2, 3], regulatory mechanisms must operate in people who inflict painful procedures in their practice with patient populations in order to prevent their distress from impairing their ability to be of assistance. In this functional magnetic resonance imaging MRI study, physicians who practice acupuncture were compared to naive participants while observing animated visual stimuli depicting needles being inserted into different body parts, including the mouth region, hands, and feet. Results indicate that the anterior insula somatosensory cortex, periaqueducal gray, and anterior cingulate cortex were significantly activated in the control group, but not in the expert group, who instead showed activation of the medial and superior prefrontal cortices and the temporoparietal junction, involved in emotion regulation and theory of mind.