Search

Funder: Shanghai Clinical Research Center for Mental Health (19MC1911100). SJTU Trans-med Awards Research (2019015) to BMS., Funder: Shanghai Clinical Research Center for Mental Health (19MC1911100). CCZ is supported by the fellowship of Shanghai Research Center for Brain Science and Brain-Inspired Technology., Deep brain stimulation (DBS) of structures in the brain's reward system is a promising therapeutic option for patients with treatment-resistant depression (TRD). Recently, DBS of the habenula (HB) in the brain's anti-reward system has also been reported to alleviate depressive symptoms in patients with TRD or bipolar disorder (BD). In this pilot open-label prospective study, we explored the safety and clinical effectiveness of HB-DBS treatment in seven patients with TRD or BD. Also, local field potentials (LFPs) were recorded from the patients' left and right HB to explore the power and asymmetry of oscillatory activities as putative biomarkers of the underlying disease state. At 1-month follow-up (FU), depression and anxiety symptoms were both reduced by 49% (n = 7) along with substantial improvements in patients' health status, functional impairment, and quality of life. Although the dropout rate was high and large variability in clinical response existed, clinical improvements were generally maintained throughout the study [56%, 46%, and 64% reduction for depression and 61%, 48%, and 70% reduction for anxiety at 3-month FU (n = 5), 6-month FU (n = 5), and 12-month FU (n = 3), respectively]. After HB-DBS surgery, sustained improvements in mania symptoms were found in two patients who presented with mild hypomania at baseline. Another patient, however, experienced an acute manic episode 2 months after surgery that required hospitalization. Additionally, weaker and more symmetrical HB LFP oscillatory activities were associated with more severe depression and anxiety symptoms at baseline, in keeping with the hypothesis that HB dysfunction contributes to MDD pathophysiology. These preliminary findings indicate that HB-DBS may offer a valuable treatment option for depressive symptoms in patients who suffer from TRD or BD. Larger and well-controlled studies are warranted to examine the safety and efficacy of HB-DBS for treatment-refractory mood disorders in a more rigorous fashion.

The habenula is an epithalamic structure implicated in negative reward mechanisms and plays a downstream modulatory role in regulation of dopaminergic and serotonergic functions. Human and animal studies show its hyperactivity in depression which is curtailed by the antidepressant response of ketamine. Deep brain stimulation of habenula (DBS) for major depression have also shown promising results. However, direct neuronal activity of habenula in human studies have rarely been reported. Here, in a cross-sectional design, we acquired both spontaneous resting state and emotional task-induced neuronal recordings from habenula from treatment resistant depressed patients undergoing DBS surgery. We first characterise the aperiodic component (1/f slope) of the power spectrum, interpreted to signify excitation-inhibition balance, in resting and task state. This aperiodicity for left habenula correlated between rest and task and which was significantly positively correlated with depression severity. Time-frequency responses to the emotional picture viewing task show condition differences in beta and gamma frequencies for left habenula and alpha for right habenula. Notably, alpha activity for right habenula was negatively correlated with depression severity. Overall, from direct habenular recordings, we thus show findings convergent with depression models of aberrant excitatory glutamatergic output of the habenula driving inhibition of monoaminergic systems., Medical Research Council Senior Clinical Fellowship (MR/P008747/1)

Subthalamic nucleus (STN) deep brain stimulation (DBS) can improve motor symptoms in Parkinson’s disease (PD), as well as potentially improving otherwise intractable comorbid depressive symptoms. To address the latter issue, we evaluated the severity of depressive symptoms along with the severity of motor symptoms in 18 PD patients (mean age, 58.4 ± 5.4 years; 9 males, 9 females; mean PD duration, 9.4 ± 4.4 years) with treatment-resistant depression (TRD) before and after approximately 1 year of STN-DBS treatment. Moreover, to gain more insight into the brain mechanism mediating the therapeutic action of STN-DBS, we utilized 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) to assess cerebral regional glucose metabolism in the patients at baseline and 1-year follow-up. Additionally, the baseline PET data from patients were compared with PET data from an age- and sex-matched control group of 16 healthy volunteers. Among them, 12 PD patients underwent post-operative follow-up PET scans. Results showed that the severity of both motor and depressive symptoms in patients with PD-TRD was reduced significantly at 1-year follow-up. Also, patients used significantly less antiparkinsonian medications and antidepressants at 1-year follow-up, as well as experiencing improved daily functioning and a better quality of life. Moreover, relative to the PET data from healthy controls, PD-TRD patients displayed widespread abnormalities in cerebral regional glucose metabolism before STN-DBS treatment, which were partially recovered at 1-year follow-up. Additionally, significant correlations were observed between the patients’ improvements in depressive symptoms following STN-DBS and post-operative changes in glucose metabolism in brain regions implicated in emotion regulation. These results support the view that STN-DBS provides a promising treatment option for managing both motor and depressive symptoms in patients who suffer from PD with TRD. However, the results should be interpreted with caution due to the observational nature of the study, small sample size, and relatively short follow-up.

ObjectivesIn this study, we sought to investigate structural imaging alterations of patients with idiopathic dystonia at the cortical and subcortical levels. The common and specific changes in two subtypes of dystonia, cervical dystonia (CD) and generalized dystonia (GD), were intended to be explored. Additionally, we sought to identify the morphometric measurements which might be related to patients' clinical characteristics, thus providing more clues of specific brain regions involved in the mechanism of idiopathic dystonia.Methods3D T1-weighted MRI scans were acquired from 56 patients with idiopathic dystonia and 30 healthy controls (HC). Patients were classified as CD or GD, according to the distinct symptom distributions. Cortical thickness (CT) of 30 CD and 26 GD were estimated and compared to HCs using Computational Anatomy Toolbox (CAT12), while volumes of subcortical structures and their shape alterations (29 CD, 25 GD, and 27 HCs) were analyzed via FSL software. Further, we applied correlation analyses between the above imaging measurements with significant differences and patients' clinical characteristics.ResultsThe results of comparisons between the two patient groups and HCs were highly consistent, demonstrating increased CT of bilateral postcentral, superiorparietal, superiorfrontal/rostralmiddlefrontal, occipital gyrus, etc., and decreased CT of bilateral cingulate, insula, entorhinal, and fusiform gyrus (PFWE < 0.005 at the cluster level). In CD, trends of negative correlations were found between disease severity and CT alterations mostly located in pre/postcentral, rostralmiddlefrontal, superiorparietal, and supramarginal regions. Besides, volumes of bilateral putamen, caudate, and thalamus were significantly reduced in both patient groups, while pallidum volume reduction was also presented in GD compared to HCs. Caudate volume reduction had a trend of correlation to increasing disease severity in GD. Last, shape analysis directly demonstrated regional surface alterations in bilateral thalamus and caudate, where the atrophy located in the head of caudate had a trend of correlation to earlier ages of onset in GD.ConclusionsOur study demonstrates wide-spread morphometric changes of CT, subcortical volumes, and shapes in idiopathic dystonia. CD and GD presented similar patterns of morphometric abnormalities, indicating shared underlying mechanisms in two different disease forms. Especially, the clinical associations of CT of multiple brain regions with disease severity, and altered volume/shape of caudate with disease severity/age of onset separately in CD and GD might serve as potential biomarkers for further disease exploration.

Interventional magnetic resonance imaging (i-MRI) for surgical guidance could help visualize the interventional process such as deep brain stimulation (DBS), improving the surgery performance and patient outcome. Different from retrospective reconstruction in conventional dynamic imaging, i-MRI for DBS has to acquire and reconstruct the interventional images sequentially online. Here we proposed a convolutional long short-term memory (Conv-LSTM) based recurrent neural network (RNN), or ConvLR, to reconstruct interventional images with golden-angle radial sampling. By using an initializer and Conv-LSTM blocks, the priors from the pre-operative reference image and intra-operative frames were exploited for reconstructing the current frame. Data consistency for radial sampling was implemented by a soft-projection method. To improve the reconstruction accuracy, an adversarial learning strategy was adopted. A set of interventional images based on the pre-operative and post-operative MR images were simulated for algorithm validation. Results showed with only 10 radial spokes, ConvLR provided the best performance compared with state-of-the-art methods, giving an acceleration up to 40 folds. The proposed algorithm has the potential to achieve real-time i-MRI for DBS and can be used for general purpose MR-guided intervention.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. TS usually co-occurs with one or multiple psychiatric disorders. Although behavioral and pharmacological treatments for TS are available, some patients do not respond to the available treatments. For these patients, TS is a severe, chronic, and disabling disorder. In recent years, deep brain stimulation (DBS) of basal ganglia-thalamocortical networks has emerged as a promising intervention for refractory TS with or without psychiatric comorbidities. Three major challenges need to be addressed to move the field of DBS treatment for TS forward: (1) patient and DBS target selection, (2) ethical concerns with treating pediatric patients, and (3) DBS treatment optimization and improvement of individual patient outcomes (motor and phonic tics, as well as functioning and quality of life). The Tourette Association of America and the American Academy of Neurology have recently released their recommendations regarding surgical treatment for refractory TS. Here, we describe the challenges, advancements, and promises of the use of DBS in the treatment of TS. We summarize the results of clinical studies and discuss the ethical issues involved in treating pediatric patients. Our aim is to provide a better understanding of the feasibility, safety, selection process, and clinical effectiveness of DBS treatment for select cases of severe and medically intractable TS.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. TS usually co-occurs with one or multiple psychiatric disorders. Although behavioral and pharmacological treatments for TS are available, some patients do not respond to the available treatments. For these patients, TS is a severe, chronic, and disabling disorder. In recent years, deep brain stimulation (DBS) of basal ganglia-thalamocortical networks has emerged as a promising intervention for refractory TS with or without psychiatric comorbidities. Three major challenges need to be addressed to move the field of DBS treatment for TS forward: (1) patient and DBS target selection, (2) ethical concerns with treating pediatric patients, and (3) DBS treatment optimization and improvement of individual patient outcomes (motor and phonic tics, as well as functioning and quality of life). The Tourette Association of America and the American Academy of Neurology have recently released their recommendations regarding surgical treatment for refractory TS. Here, we describe the challenges, advancements, and promises of the use of DBS in the treatment of TS. We summarize the results of clinical studies and discuss the ethical issues involved in treating pediatric patients. Our aim is to provide a better understanding of the feasibility, safety, selection process, and clinical effectiveness of DBS treatment for select cases of severe and medically intractable TS.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. TS usually co-occurs with one or multiple psychiatric disorders. Although behavioral and pharmacological treatments for TS are available, some patients do not respond to the available treatments. For these patients, TS is a severe, chronic, and disabling disorder. In recent years, deep brain stimulation (DBS) of basal ganglia-thalamocortical networks has emerged as a promising intervention for refractory TS with or without psychiatric comorbidities. Three major challenges need to be addressed to move the field of DBS treatment for TS forward: (1) patient and DBS target selection, (2) ethical concerns with treating pediatric patients, and (3) DBS treatment optimization and improvement of individual patient outcomes (motor and phonic tics, as well as functioning and quality of life). The Tourette Association of America and the American Academy of Neurology have recently released their recommendations regarding surgical treatment for refractory TS. Here, we describe the challenges, advancements, and promises of the use of DBS in the treatment of TS. We summarize the results of clinical studies and discuss the ethical issues involved in treating pediatric patients. Our aim is to provide a better understanding of the feasibility, safety, selection process, and clinical effectiveness of DBS treatment for select cases of severe and medically intractable TS.

Funder: Guangci Professorship Program, OBJECTIVES: Surgical procedures targeting the anterior limb of the internal capsule (aLIC) can be effective in patients with selected treatment-refractory obsessive-compulsive disorder (OCD). The aLIC consists of white-matter tracts connecting cortical and subcortical structures and show a topographical organisation. Here we assess how aLIC streamlines are affected in OCD compared with healthy controls (HCs) and which streamlines are related with post-capsulotomy improvement. METHODS: Diffusion-weighted MRI was used to compare white-matter microstructure via the aLIC between patients with OCD (n=100, 40 women, mean of age 31.8 years) and HCs (n=88, 39 women, mean of age 29.6 years). For each individual, the fractional anisotropy (FA) and streamline counts were calculated for each white-matter fibre bundle connecting a functionally defined prefrontal and subcortical region. Correlations between tractography measures and pre-capsulotomy and post-capsulotomy clinical outcomes (in obsessive-compulsive, anxiety and depression scores 6 months after surgery) were assessed in 41 patients with OCD. RESULTS: Hierarchical clustering dendrograms show an aLIC organisation clustering lateral and dissociating ventral and dorsal prefrontal-thalamic streamlines, findings highly relevant to surgical targeting. Compared with HCs, patients with OCD had lower aLIC FA across multiple prefrontal cortical-subcortical regions (p

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. TS usually co-occurs with one or multiple psychiatric disorders. Although behavioral and pharmacological treatments for TS are available, some patients do not respond to the available treatments. For these patients, TS is a severe, chronic, and disabling disorder. In recent years, deep brain stimulation (DBS) of basal ganglia-thalamocortical networks has emerged as a promising intervention for refractory TS with or without psychiatric comorbidities. Three major challenges need to be addressed to move the field of DBS treatment for TS forward: (1) patient and DBS target selection, (2) ethical concerns with treating pediatric patients, and (3) DBS treatment optimization and improvement of individual patient outcomes (motor and phonic tics, as well as functioning and quality of life). The Tourette Association of America and the American Academy of Neurology have recently released their recommendations regarding surgical treatment for refractory TS. Here, we describe the challenges, advancements, and promises of the use of DBS in the treatment of TS. We summarize the results of clinical studies and discuss the ethical issues involved in treating pediatric patients. Our aim is to provide a better understanding of the feasibility, safety, selection process, and clinical effectiveness of DBS treatment for select cases of severe and medically intractable TS.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. TS usually co-occurs with one or multiple psychiatric disorders. Although behavioral and pharmacological treatments for TS are available, some patients do not respond to the available treatments. For these patients, TS is a severe, chronic, and disabling disorder. In recent years, deep brain stimulation (DBS) of basal ganglia-thalamocortical networks has emerged as a promising intervention for refractory TS with or without psychiatric comorbidities. Three major challenges need to be addressed to move the field of DBS treatment for TS forward: (1) patient and DBS target selection, (2) ethical concerns with treating pediatric patients, and (3) DBS treatment optimization and improvement of individual patient outcomes (motor and phonic tics, as well as functioning and quality of life). The Tourette Association of America and the American Academy of Neurology have recently released their recommendations regarding surgical treatment for refractory TS. Here, we describe the challenges, advancements, and promises of the use of DBS in the treatment of TS. We summarize the results of clinical studies and discuss the ethical issues involved in treating pediatric patients. Our aim is to provide a better understanding of the feasibility, safety, selection process, and clinical effectiveness of DBS treatment for select cases of severe and medically intractable TS.

Tourette syndrome (TS) is a childhood-onset neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. TS usually co-occurs with one or multiple psychiatric disorders. Although behavioral and pharmacological treatments for TS are available, some patients do not respond to the available treatments. For these patients, TS is a severe, chronic, and disabling disorder. In recent years, deep brain stimulation (DBS) of basal ganglia-thalamocortical networks has emerged as a promising intervention for refractory TS with or without psychiatric comorbidities. Three major challenges need to be addressed to move the field of DBS treatment for TS forward: (1) patient and DBS target selection, (2) ethical concerns with treating pediatric patients, and (3) DBS treatment optimization and improvement of individual patient outcomes (motor and phonic tics, as well as functioning and quality of life). The Tourette Association of America and the American Academy of Neurology have recently released their recommendations regarding surgical treatment for refractory TS. Here, we describe the challenges, advancements, and promises of the use of DBS in the treatment of TS. We summarize the results of clinical studies and discuss the ethical issues involved in treating pediatric patients. Our aim is to provide a better understanding of the feasibility, safety, selection process, and clinical effectiveness of DBS treatment for select cases of severe and medically intractable TS.

Presentación realizada en: ECMWF/EUMETSAT NWP SAF Workshop on the treatment of random and systematic errors in satellite data assimilation for NWP, celebrado de manera virtual, del 2 al 5 de noviembre de 2020.

The subthalamic nucleus (STN) is a common target for deep brain stimulation (DBS) treatment in Parkinson's disease (PD) but much less frequently targeted for other disorders. Here we report the results of simultaneous local field potential (LFP) recordings and magnetoencephalography (MEG) in a single patient who was implanted bilaterally in the STN for the treatment of dystonia induced by chorea-acanthocytosis. Consistent with the previous results in PD, the dystonia patient showed significant subthalamo-cortical coherence in the high beta band (28-35 Hz) on both sides localized to the mesial sensorimotor areas. In addition, on the right side, significant coherence was found in the theta-alpha band (4-12 Hz) that localized to the medial prefrontal cortex with the peak in the anterior cingulate gyrus. Comparison of STN power spectra with a previously reported PD cohort showed increased power in the theta and alpha bands and decreased power in the low beta band in dystonia which is consistent with most of the previous studies. The present report extends the range of disorders for which cortico-subthalamic oscillatory connectivity has been characterized. Our results strengthen the evidence that at least some of the subthalamo-cortical oscillatory coherent networks are a feature of the healthy brain, although we do not rule out that coherence magnitude could be affected by disease.

Este es un informe dentro del Programa para la Investigación del Clima Mundial (World Climate Research Programme, WCRP) cuya misión es facilitar el análisis y la predicción de la variabilidad de la Tierra para proporcionar un valor añadido a la sociedad a nivel práctica. La WCRP tiene varios proyectos centrales, de los cuales el de Intercambio Global de Energía y Agua (Global Energy and Water Exchanges, GEWEX) es uno de ellos. Este proyecto se centra en estudiar el ciclo hidrológico global y regional, así como sus interacciones a través de la radiación y energía y sus implicaciones en el cambio global. Dentro de GEWEX existe el proyecto de Evaluación del Vapor de Agua (VAP, Water Vapour Assessment) que estudia las medidas de concentraciones de vapor de agua en la atmósfera, sus interacciones radiativas y su repercusión en el cambio climático global. El vapor de agua es, de largo, el gas invernadero más importante que reside en la atmósfera. Es, potencialmente, la causa principal de la amplificación del efecto invernadero causado por emisiones de origen humano (principalmente el CO2). Las medidas precisas de su concentración en la atmósfera son determinantes para cuantificar este efecto de retroalimentación positivo al cambio climático. Actualmente, se está lejos de tener medidas de concentraciones de vapor de agua suficientemente precisas para sacar conclusiones significativas de dicho efecto. El informe del WCRP titulado "GEWEX water vapor assessment. Final Report" detalla el estado actual de las medidas de las concentraciones de vapor de agua en la atmósfera. AEMET ha colaborado en la generación de este informe y tiene a unos de sus miembros, Xavier Calbet, como co-autor de este informe.

Based on the annual variation of the rainfall departure percentage in summer in the lower-middle reaches of the Yangtze River and the Huaihe River valley, 7 cases for the abnormal drought and flooding summers (the drought years: 1981, 1984, 1985; the flooding years: 1980, 1982, 1983, 1987) are selected. First we analyse the general circulation characteristics of the summer drought and flooding, and then the evolution processes of the general circulation patterns from preceding winters to summers are studied. It is found that during the two kinds of preceding winters for the drought and flooding summer, not only the general circulation patterns in the high-mid latitudes, the local Hadley cells in East Asia but also the activities of the cold surge in the lower latitude are different obviously. Spring, especially April, is the turning period of the general circulation in preceding winter for the drought or flooding summer evolution towards opposite direction. Hereafter, the drought or flooding circulation pattern is established and developed.

Introduction: Deep brain stimulation (DBS) studies in Parkinson’s Disease (PD) targeting subthalamic nucleus (STN) have characterized its spectral properties across cognitive processes. In emotional evaluation tasks, specific alpha frequency (8-12 Hz) event related de-synchronization (ERD) (reduced power) has been demonstrated. Time locked stimulation of STN relative to stimuli onset have shown subjective positive valence shifts with 10 Hz but not with 130 Hz. However, neurophysiological effects of stimulation itself on power modulation have not been investigated. We aim to investigate effects of acute stimulation of right STN on concurrent power modulation in the contralateral STN and frontal scalp EEG. From our previous work, we had a strong a priori hypothesis that negative imagery without stimulation would be associated with alpha ERD; negative imagery with 130 Hz stimulation also associated with alpha ERD given the lack of its effect on subjective valence ratings; negative imagery with 10 Hz stimulation to be associated with enhanced alpha power given the shift in behavioural valence ratings. Methods: Twenty-four subjects with STN DBS underwent emotional picture viewing tasks comprising neutral and negative pictures. In a subset of these subjects, the negative images were associated with time-locked acute stimulation at either 10 Hz or 130 Hz. Power of signals were estimated relative to the baseline and subjected to non-parametric statistical testing. Results: As hypothesized, in 130 Hz stimulation condition, we show a decrease in alpha power to negative versus neutral images irrespective of stimulation. In contrast, this alpha power decrease was no longer evident in the negative 10 Hz stimulation condition consistent with a predicted increase in alpha power. Greater beta power in the 10 Hz stimulation condition along with correlations between beta power across the 10 Hz stimulation and unstimulated conditions suggest physiological and cognitive generalization effects. Conclusions: Acute alpha specific frequency stimulation presumably was associated with a loss of this expected decrease or desynchronization in alpha power to negative images suggesting the capacity to facilitate the synchronization of alpha and enhance power. Acute time locked stimulation has the potential to provide causal insights about the spectral frequencies and temporal dynamics of emotional processing.

Peer reviewed: True, Acknowledgements: We thank Dr Lifu Deng and Dr. Tianzhu Xiong for valuable advice on imaging data processing., BACKGROUND: Though deep brain stimulation (DBS) shows increasing potential in treatment-resistant depression (TRD), the underlying neural mechanisms remain unclear. Here, we investigated functional and structural connectivities related to and predictive of clinical effectiveness of DBS at ventral capsule/ventral striatum region for TRD. METHODS: Stimulation effects of 71 stimulation settings in 10 TRD patients were assessed. The electric fields were estimated and combined with normative functional and structural connectomes to identify connections as well as fibre tracts beneficial for outcome. We calculated stimulation-dependent optimal connectivity and constructed models to predict outcome. Leave-one-out cross-validation was used to validate the prediction value. RESULTS: Successful prediction of antidepressant effectiveness in out-of-sample patients was achieved by the optimal connectivity profiles constructed with both the functional connectivity (R=0.49 at p

The amygdala, orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) form a crucial part of the emotion circuit, yet their emotion induced responses and interactions have been poorly investigated with direct intracranial recordings. Such high-fidelity signals can uncover precise spectral dynamics and frequency differences in valence processing allowing novel insights on neuromodulation. Here, leveraging the unique spatio-temporal advantages of intracranial electroencephalography (iEEG) from a cohort of 35 patients with intractable epilepsy (with 71 contacts in amygdala, 31 in OFC and 43 in mPFC), we assessed the spectral dynamics and interactions between the amygdala, OFC and mPFC during an emotional picture viewing task. Task induced activity showed greater broadband gamma activity in the negative condition compared to positive condition in all the three regions. Similarly, beta activity was increased in the negative condition in the amygdala and OFC while decreased in mPFC. Furthermore, beta activity of amygdala showed significant negative association with valence ratings. Critically, model-based computational analyses revealed unidirectional connectivity from mPFC to the amygdala and bidirectional communication between OFC-amygdala and OFC-mPFC. Our findings provide direct neurophysiological evidence for a much-posited model of top-down influence of mPFC over amygdala and a bidirectional influence between OFC and the amygdala. Altogether, in a relatively large sample size with human intracranial neuronal recordings, we highlight valence-dependent spectral dynamics and dyadic coupling within the amygdala-mPFC-OFC network with implications for potential targeted neuromodulation in emotion processing.