Neural correlates of anxiety in adult-onset isolated dystonia.

Psychiatric disturbances are commonly associated with adult-onset isolated dystonia (AOID); however, the mechanisms underlying psychiatric abnormalities in AOID remain unknown. We aimed to investigate the structural and functional brain changes in AOID patients with anxiety, and identify imaging biomarkers for diagnosing anxiety. Structural and functional magnetic resonance was performed on 69 AOID patients and 35 healthy controls (HCs). The Hamilton Anxiety Scale (HAMA) was used to assess anxiety symptoms in AOID patients and assign patients to AOID with and without anxiety groups. Group differences in grey matter volume, amplitude of low-frequency fluctuations (ALFF), fractional ALFF, and regional homogeneity (ReHo) were evaluated. Area under the receiver operating characteristic curve (ROC AUC) was used as a metric to identify imaging biomarkers for diagnosing anxiety. AOID patients with anxiety exhibited an increased ALFF and ReHo in the left angular gyrus (ANG.L) compared with those without and HCs (voxel P<0.001 and cluster P<0.05, corrected using GRF). A significant positive correlation was observed between ALFF (r = 0.627, P<0.001) and ReHo (r = 0.515, P<0.001) in the ANG.L and HAMA scores in AOID patients. ALFF and ReHo in the ANG.L exhibited an ROC AUC of 0.904 and 0.851, respectively, in distinguishing AOID patients with anxiety from those without and an ROC AUC of 0.887 and 0.853, respectively, in distinguishing AOID patients with anxiety from HCs. These findings provide new insights into the pathophysiology of psychiatric disturbances and highlight potential candidate biomarkers for identifying anxiety in AOID patients.

Differential bioaccumulation and tolerances of massive and branching scleractinian corals to polycyclic aromatic hydrocarbons in situ.

Scleractinian corals are capable of accumulating polycyclic aromatic hydrocarbons (PAHs) in reef environments; however, the mechanism behind their PAHs tolerance is unknown. This study investigated the occurrence and bioaccumulation of PAHs in coral reef ecosystems and examined the physiological responses induced by PAHs in coral hosts and their algal symbionts, the massive coral Galaxea fascicularis and branching coral Pocillopora damicornis. G. fascicularis had a higher PAHs accumulation capacity than P. damicornis. Both the coral hosts and algal symbionts preferentially accumulated acenaphthene, dibenzo(a,h)anthracene, and benzo(a)pyrene. The accumulated PAHs by G. fascicularis and P. damicornis hosts was accompanied by a reduction in detoxification ability. The accumulated PAHs could induce oxidative stress in P. damicorni hosts, thus G. fascicularis demonstrated a greater tolerance to PAHs compared to P. damicornis. Meanwhile, their algal symbionts had fewer physiological responses to accumulated PAHs than the coral hosts. Negative effects were not observed with benzo(a)pyrene. Taken together, these results suggest massive and branching scleractinian corals have different PAHs bioaccumulation and tolerance mechanisms, and indicate that long-term PAHs pollution could cause significant alterations of community structures in coral reef ecosystems.

Topological alterations in white matter anatomical networks in cervical dystonia.

BACKGROUND: Accumulating neuroimaging evidence indicates that patients with cervical dystonia (CD) have changes in the cortico-subcortical white matter (WM) bundle. However, whether these patients' WM structural networks undergo reorganization remains largely unclear. We aimed to investigate topological changes in large-scale WM structural networks in patients with CD compared to healthy controls (HCs), and explore the network changes associated with clinical manifestations. METHODS: Diffusion tensor imaging (DTI) was conducted in 30 patients with CD and 30 HCs, and WM network construction was based on the BNA-246 atlas and deterministic tractography. Based on the graph theoretical analysis, global and local topological properties were calculated and compared between patients with CD and HCs. Then, the AAL-90 atlas was used for the reproducibility analyses. In addition, the relationship between abnormal topological properties and clinical characteristics was analyzed. RESULTS: Compared with HCs, patients with CD showed changes in network segregation and resilience, characterized by increased local efficiency and assortativity, respectively. In addition, a significant decrease of network strength was also found in patients with CD relative to HCs. Validation analyses using the AAL-90 atlas similarly showed increased assortativity and network strength in patients with CD. No significant correlations were found between altered network properties and clinical characteristics in patients with CD. CONCLUSION: Our findings show that reorganization of the large-scale WM structural network exists in patients with CD. However, this reorganization is attributed to dystonia-specific abnormalities or hyperkinetic movements that need further identification.

Regional structural abnormalities in thalamus in idiopathic cervical dystonia.

BACKGROUND: The thalamus has a central role in the pathophysiology of idiopathic cervical dystonia (iCD); however, the nature of alterations occurring within this structure remain largely elusive. Using a structural magnetic resonance imaging (MRI) approach, we examined whether abnormalities differ across thalamic subregions/nuclei in patients with iCD. METHODS: Structural MRI data were collected from 37 patients with iCD and 37 healthy controls (HCs). Automatic parcellation of 25 thalamic nuclei in each hemisphere was performed based on the FreeSurfer program. Differences in thalamic nuclei volumes between groups and their relationships with clinical information were analysed in patients with iCD. RESULTS: Compared to HCs, a significant reduction in thalamic nuclei volume primarily in central medial, centromedian, lateral geniculate, medial geniculate, medial ventral, paracentral, parafascicular, paratenial, and ventromedial nuclei was found in patients with iCD (P < 0.05, false discovery rate corrected). However, no statistically significant correlations were observed between altered thalamic nuclei volumes and clinical characteristics in iCD group. CONCLUSION: This study highlights the neurobiological mechanisms of iCD related to thalamic volume changes.

Progressive thalamic nuclear atrophy in blepharospasm and blepharospasm-oromandibular dystonia.

The thalamus is considered a key region in the neuromechanisms of blepharospasm. However, previous studies considered it as a single, homogeneous structure, disregarding potentially useful information about distinct thalamic nuclei. Herein, we aimed to examine (i) whether grey matter volume differs across thalamic subregions/nuclei in patients with blepharospasm and blepharospasm-oromandibular dystonia; (ii) causal relationships among abnormal thalamic nuclei; and (iii) whether these abnormal features can be used as neuroimaging biomarkers to distinguish patients with blepharospasm from blepharospasm-oromandibular dystonia and those with dystonia from healthy controls. Structural MRI data were collected from 56 patients with blepharospasm, 20 with blepharospasm-oromandibular dystonia and 58 healthy controls. Differences in thalamic nuclei volumes between groups and their relationships to clinical information were analysed in patients with dystonia. Granger causality analysis was employed to explore the causal effects among abnormal thalamic nuclei. Support vector machines were used to test whether these abnormal features could distinguish patients with different forms of dystonia and those with dystonia from healthy controls. Compared with healthy controls, patients with blepharospasm exhibited reduced grey matter volume in the lateral geniculate and pulvinar inferior nuclei, whereas those with blepharospasm-oromandibular dystonia showed decreased grey matter volume in the ventral anterior and ventral lateral anterior nuclei. Atrophy in the pulvinar inferior nucleus in blepharospasm patients and in the ventral lateral anterior nucleus in blepharospasm-oromandibular dystonia patients was negatively correlated with clinical severity and disease duration, respectively. The proposed machine learning scheme yielded a high accuracy in distinguishing blepharospasm patients from healthy controls (accuracy: 0.89), blepharospasm-oromandibular dystonia patients from healthy controls (accuracy: 0.82) and blepharospasm from blepharospasm-oromandibular dystonia patients (accuracy: 0.94). Most importantly, Granger causality analysis revealed that a progressive driving pathway from pulvinar inferior nuclear atrophy extends to lateral geniculate nuclear atrophy and then to ventral lateral anterior nuclear atrophy with increasing clinical severity in patients with blepharospasm. These findings suggest that the pulvinar inferior nucleus in the thalamus is the focal origin of blepharospasm, extending to pulvinar inferior nuclear atrophy and subsequently extending to the ventral lateral anterior nucleus causing involuntary lower facial and masticatory movements known as blepharospasm-oromandibular dystonia. Moreover, our results also provide potential targets for neuromodulation especially deep brain stimulation in patients with blepharospasm and blepharospasm-oromandibular dystonia.

Abnormal supplementary motor areas are associated with idiopathic and acquired blepharospasm.

Blepharospasm is a common form of focal dystonia characterized by excessive and involuntary spasms of the orbicularis oculi. In addition to idiopathic blepharospasm, lesions in various brain regions can also cause acquired blepharospasm. Whether these two types of blepharospasm share a common brain network remains largely unknown. Herein, we performed lesion coactivation network mapping, based on meta-analytic connectivity modeling, to test whether lesions causing blepharospasm could be mapped to a common coactivation brain network. We then tested the abnormality of the network in patients with idiopathic blepharospasm (n = 42) compared with healthy controls (n = 44). We identified 21 cases of lesion-induced blepharospasms through a systematic literature search. Although these lesions were heterogeneous, they were part of a co-activated brain network that mainly included the bilateral supplementary motor areas. Coactivation of these regions defines a single brain network that encompasses or is adjacent to most heterogeneous lesions causing blepharospasm. Moreover, the bilateral supplementary motor area is primarily associated with action execution, visual motion, and imagination, and participates in finger tapping and saccades. They also reported decreased functional connectivity with the left posterior cingulate cortex in patients with idiopathic blepharospasm. These results demonstrate a common convergent abnormality of the supplementary motor area across idiopathic and acquired blepharospasms, providing additional evidence that the supplementary motor area is an important brain region that is pathologically impaired in patients with blepharospasm.

Neural Correlates of Facial Emotion Recognition Impairment in Blepharospasm: A Functional Magnetic Resonance Imaging Study.

Selective impairment in recognizing facial expressions of disgust was reported in patients with focal dystonia several years ago, but the basic neural mechanisms remain largely unexplored. Therefore, we investigated whether dysfunction of the brain network involved in disgust recognition processing was related to this selective impairment in blepharospasm. Facial emotion recognition evaluations and resting-state functional magnetic resonance imaging were performed in 33 blepharospasm patients and 33 healthy controls (HCs). The disgust processing network was constructed, and modularity analyses were performed to identify sub-networks. Regional functional indexes and intra- and inter-functional connections were calculated and compared between the groups. Compared to HCs, blepharospasm patients demonstrated a worse performance in disgust recognition. In addition, functional connections within the sub-network involved in perception processing rather than recognition processing of disgust were significantly decreased in blepharospasm patients compared to HCs. Specifically, decreased functional connections were noted between the left fusiform gyrus (FG) and right middle occipital gyrus (MOG), the left FG and right FG, and the right FG and left MOG. We identified decreased functional activity in these regions, as indicated by a lower amplitude of low-frequency fluctuation in the left MOG, fractional amplitude of low-frequency fluctuation in the right FG, and regional homogeneity in the right FG and left MOG in blepharospasm patients versus HCs. Our results suggest that dysfunctions of the disgust processing network exist in blepharospasm. A deficit in disgust emotion recognition may be attributed to disturbances in the early perception of visual disgust stimuli in blepharospasm patients.

Supplementary motor area driving changes of structural brain network in blepharospasm.

Blepharospasm is traditionally thought to be a movement disorder that results from basal ganglia dysfunction. Recently, accumulating morphometric studies have revealed structural alterations outside the basal ganglia, such as in the brainstem, cerebellum and sensorimotor cortex, suggesting that blepharospasm may result from network disorders. However, the temporal and causal relationships between structural alterations and whether there are disease duration-related hierarchical structural changes in these patients remain largely unknown. Structural MRI was performed in 62 patients with blepharospasm, 62 patients with hemifacial spasm and 62 healthy controls to assess the structural alterations using voxel-based morphology and structural covariance networks. The use of the causal structural covariance network, modularity analysis and functional decoding were subsequently performed to map the causal effect of grey matter change pattern, hierarchical topography and functional characterizations of the structural network throughout the disease duration of blepharospasm. Greater grey matter volume in the left and right supplementary motor areas was identified in patients with blepharospasm compared to that in patients with hemifacial spasm and healthy controls, whereas no significant difference was identified between patients with hemifacial spasm and healthy controls. In addition, increased grey matter volume covariance between the right supplementary motor area and right brainstem, left superior frontal gyrus, left supplementary motor area and left paracentral gyrus was found in patients with blepharospasm compared to healthy controls. Further causal structural covariance network, modularity analysis and functional decoding showed that the right supplementary motor area served as a driving core in patients with blepharospasm, extending greater grey matter volume to areas in the cortico-basal ganglia-brainstem motor pathway and cortical regions in the vision-motor integration pathway. Taken together, our results suggest that the right supplementary motor area is an early and important pathologically impaired region in patients with blepharospasm. With a longer duration of blepharospasm, increased grey matter volume extends from the right supplementary motor area to the cortico-basal ganglia motor and visual-motor integration pathways, showing a hierarchy of structural abnormalities in the disease progression of blepharospasm, which provides novel evidence to support the notion that blepharospasm may arise from network disorders and is associated with a wide range of grey matter abnormalities.

Interactive effects of acidification and copper exposure on the reproduction and metabolism of coral endosymbiont Cladocopium goreaui.

Ocean acidification resulting from increased CO2 and pollution from land-sourced toxicants such as copper have been linked to coral cover declines in coastal reef ecosystems. The impacts of ocean acidification and copper pollution on corals have been intensively investigated, whereas research on their effects on coral endosymbiont Symbiodiniaceae is limited. In this study, reproduction, photosynthetic parameters, nutrient accumulation and metabolome of Symbiodiniaceae Cladocopium goreaui were investigated after a weeklong treatment with acute CO2-induced acidification and copper ion. Acidification promoted algal reproduction through increased nutrients assimilation, upregulated citrate cycle and biomolecular biosynthesis pathway, while copper exposure repressed algal reproduction through toxic effects. The combined acidification and copper exposure caused the same decline in algal reproduction as copper exposure alone, but the upregulation of pentose phosphate pathway and the downregulation of aromatic amino acid biosynthesis. These results suggest that copper pollution could override the positive effects of acidification on the symbiodiniacean reproduction.

Unraveling the metabolic effects of benzophenone-3 on the endosymbiotic dinoflagellate Cladocopium goreaui.

As a well-known pseudo-persistent environmental pollutant, oxybenzone (BP-3) and its related organic ultraviolet (UV) filters have been verified to directly contribute to the increasing mortality rate of coral reefs. Previous studies have revealed the potential role of symbiotic Symbiodiniaceae in protecting corals from the toxic effects of UV filters. However, the detailed protection mechanism(s) have not been explained. Here, the impacts of BP-3 on the symbiotic Symbiodiniaceae Cladocopium goreaui were explored. C. goreaui cells exhibited distinct cell growth at different BP-3 doses, with increasing growth at the lower concentration (2 mg L-1) and rapid death at a higher concentration (20 mg L-1). Furthermore, C. goreaui cells showed a significant BP-3 uptake at the lower BP-3 concentration. BP-3 absorbing cells exhibited elevated photosynthetic efficiency, and decreased cellular carbon and nitrogen contents. Besides, the derivatives of BP-3 and aromatic amino acid metabolism highly responded to BP-3 absorption and biodegradation. Our physiological and metabolic results reveal that the symbiotic Symbiodiniaceae could resist the toxicity of a range of BP-3 through promoting cell division, photosynthesis, and reprogramming amino acid metabolism. This study provides novel insights into the influences of organic UV filters to coral reef ecosystems, which urgently needs increasing attention and management.

Population-Average Brain Templates and Application to Automated Voxel-Wise Analysis Pipelines for Cynomolgus Macaque.

The growing number of neuroimaging studies of cynomolgus macaques require extending existing templates to facilitate species-specific application of voxel-wise neuroimaging methodologies. This study aimed to create population-averaged structural magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) templates for the cynomolgus macaques and apply the templates in fully automated voxel-wise analyses. We presented the development of symmetric and asymmetric MRI and DTI templates from a sample of 63 young male cynomolgus monkeys with the use of optimized template creation approaches. We also generated the associated average tissue probability maps and Diffeomorphic Anatomical Registration using Exponentiated Lie Algebra templates for use with the Statistical Parametric Mapping (SPM), as well as the average fractional anisotropy/skeleton targets for incorporation into tract-based spatial statistics (TBSS) framework. Both asymmetric and symmetric templates in a standardized coordinate space demonstrated low bias and high contrast. Fully automated processing using SPM was accomplished for all native MRI datasets and demonstrated outstanding performance regarding skull-stripping, segmentation, and normalization when using the MRI templates. Automated normalization to the DTI template was excellently achieved for all native DTI images using the TBSS pipeline. The cynomolgus MRI and DTI templates are anticipated to provide a common platform for precise single-subject data analysis and facilitate comparison of neuroimaging findings in cynomolgus monkeys across studies and sites. It is also hoped that the procedures of template creation and fully-automated voxel-wise frameworks will provide a straightforward avenue for investigating brain function, development, and neuro-psychopathological disorders in non-human primate models.

Topological Alterations in White Matter Structural Networks in Blepharospasm.

BACKGROUND: Accumulating evidence indicates regional structural changes in the white matter (WM) of brains in patients with blepharospasm (BSP); however, whether large-scale WM structural networks undergo widespread reorganization in these patients remains unclear. OBJECTIVE: We investigated topology changes and global and local features of large-scale WM structural networks in BSP patients compared with hemifacial spasm (HFS) patients or healthy controls (HCs). METHODS: This cross-sectional study applied graph theoretical analysis to assess deterministic diffusion tensor tractography findings in 41 BSP patients, 41 HFS patients, and 41 HCs. WM structural connectivity in 246 cortical and subcortical regions was assessed, and topological parameters of the resulting graphs were calculated. Networks were compared among BSP, HFS, and HCs groups. RESULTS: Compared to HCs, both BSP and HFS patients showed alterations in network integration and segregation characterized by increased global efficiency and modularity and reduced shortest path length. Moreover, increased nodal efficiency in multiple cortical and subcortical regions was found in BSP and HFS patients compared with HCs. However, these differences were not found between BSP and HFS patients. Whereas all participants showed highly similar hub distribution patterns, BSP patients had additional hub regions not present in either HFS patients or HCs, which were located in the primary head and face motor cortex and basal ganglia. CONCLUSIONS: Our findings suggest that the large-scale WM structural network undergoes an extensive reorganization in BSP, probably due to both dystonia-specific abnormalities and facial hyperkinetic movements. © 2021 International Parkinson and Movement Disorder Society.

Machine Learning for Predicting Individual Severity of Blepharospasm Using Diffusion Tensor Imaging.

Accumulating diffusion tensor imaging (DTI) evidence suggests that white matter abnormalities evaluated by local diffusion homogeneity (LDH) or fractional anisotropy (FA) occur in patients with blepharospasm (BSP), both of which are significantly correlated with disease severity. However, whether the individual severity of BSP can be identified using these DTI metrics remains unknown. We aimed to investigate whether a combination of machine learning techniques and LDH or FA can accurately identify the individual severity of BSP. Forty-one patients with BSP were assessed using the Jankovic Rating Scale and DTI. The patients were assigned to non-functionally and functionally limited groups according to their Jankovic Rating Scale scores. A machine learning scheme consisting of beam search and support vector machines was designed to identify non-functionally versus functionally limited outcomes, with the input features being LDH or FA in 68 white matter regions. The proposed machine learning scheme with LDH or FA yielded an overall accuracy of 88.67 versus 85.19% in identifying non-functionally limited versus functionally limited outcomes. The scheme also identified a sensitivity of 91.40 versus 85.87% in correctly identifying functionally limited outcomes, a specificity of 83.33 versus 83.67% in accurately identifying non-functionally limited outcomes, and an area under the curve of 93.7 versus 91.3%. These findings suggest that a combination of LDH or FA measurements and a sophisticated machine learning scheme can accurately and reliably identify the individual disease severity in patients with BSP.