Brain StimulationPub Date : 2025-04-17DOI: 10.1016/j.brs.2025.04.009
Boshuo Wang , Aman S. Aberra
{"title":"Bridging macroscopic and microscopic modeling of electric field by brain stimulation","authors":"Boshuo Wang , Aman S. Aberra","doi":"10.1016/j.brs.2025.04.009","DOIUrl":"10.1016/j.brs.2025.04.009","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 897-899"},"PeriodicalIF":7.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain StimulationPub Date : 2025-04-17DOI: 10.1016/j.brs.2025.04.016
Alexandru D. Iordan , Victor Di Rita , Brett S. Schneider , Sami J. Barmada , Benjamin M. Hampstead
{"title":"Network-level high definition tDCS in a complex patient presentation","authors":"Alexandru D. Iordan , Victor Di Rita , Brett S. Schneider , Sami J. Barmada , Benjamin M. Hampstead","doi":"10.1016/j.brs.2025.04.016","DOIUrl":"10.1016/j.brs.2025.04.016","url":null,"abstract":"","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 882-884"},"PeriodicalIF":7.6,"publicationDate":"2025-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain StimulationPub Date : 2025-04-15DOI: 10.1016/j.brs.2025.04.015
Alexandra Katherine Isis Yonza , Lechan Tao , Xiao Zhang , Dmitry Postnov , Krzysztof Kucharz , Barbara Lind , Antonios Asiminas , Anpan Han , Victor Sonego , Kayeon Kim , Changsi Cai
{"title":"Spatially and temporally mismatched blood flow and neuronal activity by high-intensity intracortical microstimulation","authors":"Alexandra Katherine Isis Yonza , Lechan Tao , Xiao Zhang , Dmitry Postnov , Krzysztof Kucharz , Barbara Lind , Antonios Asiminas , Anpan Han , Victor Sonego , Kayeon Kim , Changsi Cai","doi":"10.1016/j.brs.2025.04.015","DOIUrl":"10.1016/j.brs.2025.04.015","url":null,"abstract":"<div><h3>Introduction</h3><div>Intracortial microstimulation (ICMS) is widely used in neuroprosthetic brain-machine interfacing, particularly in restoring lost sensory and motor functions. Spiking neuronal activity requires increased cerebral blood flow to meet local metabolic demands, a process conventionally denoted as neurovascular coupling (NVC). However, it is unknown precisely how and to what extent ICMS elicits NVC and how the neuronal and blood flow responses to ICMS correlate. Suboptimal NVC by ICMS may compromise oxygen and energy delivery to the activated neurons thus impair neuroprosthetic functionality.</div></div><div><h3>Material and method</h3><div>We used wide-field imaging (WFI), laser speckle imaging (LSI) and two-photon microscopy (TPM) to study living, transgenic mice expressing calcium (Ca<sup>2+</sup>) fluorescent indicators in either neurons or vascular mural cells (VMC), as well as to measure vascular inner lumen diameters.</div></div><div><h3>Result</h3><div>By testing a range of stimulation amplitudes and examining cortical tissue responses at different distances from the stimulating electrode tip, we found that high stimulation intensities (≥50 μA) elicited a spatial and temporal neurovascular decoupling in regions most adjacent to electrode tip (<200 μm), with significantly delayed onset times of blood flow responses to ICMS and compromised maximum blood flow increases. We attribute these effects respectively to delayed Ca<sup>2+</sup> signalling and decreased Ca<sup>2+</sup> sensitivity in VMCs.</div></div><div><h3>Conclusion</h3><div>Our study offers new insights into ICMS-associated neuronal and vascular physiology with potentially critical implications towards the optimal design of ICMS in neuroprosthetic therapies: low intensities preserve NVC; high intensities disrupt NVC responses and potentially precipitate blood supply deficits.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 885-896"},"PeriodicalIF":7.6,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143855240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain StimulationPub Date : 2025-04-11DOI: 10.1016/j.brs.2025.04.013
Theresa Ester-Nacke , Ralf Veit , Julia Thomanek , Magdalena Book , Lukas Tamble , Marie Beermann , Dorina Löffler , Ricardo Salvador , Giulio Ruffini , Martin Heni , Andreas L. Birkenfeld , Christian Plewnia , Hubert Preissl , Stephanie Kullmann
{"title":"Repeated net-tDCS of the hypothalamus appetite-control network enhances inhibitory control and decreases sweet food intake in persons with overweight or obesity","authors":"Theresa Ester-Nacke , Ralf Veit , Julia Thomanek , Magdalena Book , Lukas Tamble , Marie Beermann , Dorina Löffler , Ricardo Salvador , Giulio Ruffini , Martin Heni , Andreas L. Birkenfeld , Christian Plewnia , Hubert Preissl , Stephanie Kullmann","doi":"10.1016/j.brs.2025.04.013","DOIUrl":"10.1016/j.brs.2025.04.013","url":null,"abstract":"<div><h3>Background</h3><div>Reduced inhibitory control is associated with obesity and neuroimaging studies indicate that diminished prefrontal cortex activity influence eating behavior and metabolism. The hypothalamus regulates energy homeostasis and is functionally connected to cortical and subcortical regions especially the frontal areas.</div></div><div><h3>Objectives</h3><div>We tested network-targeted transcranial direct current stimulation (net-tDCS) to influence the excitability of brain regions involved in appetite control.</div></div><div><h3>Methods</h3><div>In a randomized, double-blind parallel group design, 44 adults with overweight or obesity (BMI 30.6 kg/m<sup>2</sup>, 52.3 % female) received active (anodal or cathodal) or sham 12-channel net-tDCS on the hypothalamus appetite-control network for 25 min on three consecutive days while performing a Stop-Signal-Task to measure response inhibition. Before and after stimulation, state questionnaires assessed changes in desire to eat and food craving. Directly after stimulation, participants received a breakfast buffet to evaluate <em>ad-libitum</em> food intake. An oral glucose tolerance test was conducted at follow-up. Resting-state functional MRI was obtained at baseline and follow-up.</div></div><div><h3>Results</h3><div>The Stop-Signal Reaction Time (SSRT) was shorter in both active groups versus sham, indicating improved response inhibition. Additionally, a stronger increase in hypothalamic functional connectivity was associated with shorter SSRT. Caloric intake of sweet food was lower in the anodal group versus sham, but no main effects between groups were observed on total and macronutrient intake, food craving ratings and desire to eat. At follow-up, no differences were observed between groups on peripheral metabolism.</div></div><div><h3>Conclusion</h3><div>Our study suggests that modulating hypothalamic functional network connectivity patterns via net-tDCS may improve food choice and inhibitory control.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 863-874"},"PeriodicalIF":7.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843231","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain StimulationPub Date : 2025-04-11DOI: 10.1016/j.brs.2025.04.011
Osama Elyamany , Jona Iffland , Josef Bak , Cornelius Classen , Guido Nolte , Till R. Schneider , Gregor Leicht , Christoph Mulert
{"title":"Predictive role of endogenous phase lags between target brain regions in dual-site transcranial alternating current stimulation","authors":"Osama Elyamany , Jona Iffland , Josef Bak , Cornelius Classen , Guido Nolte , Till R. Schneider , Gregor Leicht , Christoph Mulert","doi":"10.1016/j.brs.2025.04.011","DOIUrl":"10.1016/j.brs.2025.04.011","url":null,"abstract":"<div><h3>Background</h3><div>Dual-site transcranial alternating current stimulation (tACS) provides a promising tool for modulating interregional brain connectivity by entraining neural oscillations. However, prior studies have reported inconsistent effects on connectivity and behavioral outcomes. They often focused on individualized stimulation-frequency as a key entrainment factor, while typically not focusing on the role of endogenous phase lags. To address this gap, we explored the predictive value of endogenous phase lags in dual-site tACS to modulate interhemispheric connectivity during dichotic listening.</div></div><div><h3>Methods</h3><div>Thirty healthy participants (16 females) completed a dichotic listening task while undergoing simultaneous electroencephalography and tACS, including four bitemporal verum conditions with varying phase lags (0°, 45°, 90°, and 180°), and a sham condition across five sessions. Each session involved 20 min of 40-Hz tACS at a 0.5 mA peak-to-baseline amplitude applied to the temporal regions, with phase lags differing across sessions. Endogenous phase lags between the auditory cortices were calculated to explain changes in the laterality index (LI) across stimulation conditions by defining optimal and disruptive stimulation conditions for each participant.</div></div><div><h3>Results</h3><div>Consistent with our hypothesis, our personalized analysis based on the calculated endogenous phase lags showed a significantly lower LI during the closest (optimal) stimulation condition compared to both the sham and farthest (disruptive) conditions. Conversely, the farthest stimulation condition did not statistically increase the LI compared to sham.</div></div><div><h3>Conclusions</h3><div>These findings highlight the importance of incorporating endogenous phase dynamics into dual-site tACS protocols, paving the way for more consistent and individualized neuromodulatory interventions.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 780-793"},"PeriodicalIF":7.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143828731","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain StimulationPub Date : 2025-04-11DOI: 10.1016/j.brs.2025.04.008
Yehhyun Jo , Xiaojia Liang , Hong Hanh Nguyen , Yeonseo Choi , Minji Choi , Ga-Eun Bae , Yakdol Cho , Jiwan Woo , Hyunjoo Jenny Lee
{"title":"Selective manipulation of excitatory and inhibitory neurons in top-down and bottom-up visual pathways using ultrasound stimulation","authors":"Yehhyun Jo , Xiaojia Liang , Hong Hanh Nguyen , Yeonseo Choi , Minji Choi , Ga-Eun Bae , Yakdol Cho , Jiwan Woo , Hyunjoo Jenny Lee","doi":"10.1016/j.brs.2025.04.008","DOIUrl":"10.1016/j.brs.2025.04.008","url":null,"abstract":"<div><h3>Introduction</h3><div>Techniques for precise manipulation of neurons in specific neural pathways are crucial for excitatory/inhibitory (E/I) balance and investigation of complex brain circuits. Low-intensity focused ultrasound stimulation (LIFUS) has emerged as a promising tool for noninvasive deep-brain targeting at high spatial resolution. However, there is a lack of studies that extensively investigate the modulation of top-down and bottom-up corticothalamic circuits via selective manipulation of excitatory and inhibitory neurons. Here, a comprehensive methodology using electrophysiological recording and c-Fos staining is employed to demonstrate pulse repetition frequency (PRF)-dependent E/I selectivity of ultrasound stimulation in the top-down and bottom-up corticothalamic pathways of the visual circuit in rodents.</div></div><div><h3>Materials and methods</h3><div>Ultrasound stimulation at various PRFs is applied to either the lateral posterior nucleus of the thalamus (LP) or the primary visual cortex (V1), and multi-channel single-unit activity is recorded from the V1 using a silicon probe.</div></div><div><h3>Results and conclusion</h3><div>Our results demonstrate that high-frequency PRFs, particularly at 3 kHz and 1 kHz, are effective at activating the bidirectional corticothalamic visual pathway. In addition, brain region-specific PRFs modulate E/I cortical signals, corticothalamic projections, and synaptic neurotransmission, which is imperative for circuit-specific applications and behavioral studies.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 848-862"},"PeriodicalIF":7.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain StimulationPub Date : 2025-04-11DOI: 10.1016/j.brs.2025.04.007
Hyun-Jee Han , Hakseung Kim , Dong-Joo Kim
{"title":"Systematic review for VNS vs. pharmaceutical modulations for multifaceted neurological disorder management through cross-case, network meta-analysis","authors":"Hyun-Jee Han , Hakseung Kim , Dong-Joo Kim","doi":"10.1016/j.brs.2025.04.007","DOIUrl":"10.1016/j.brs.2025.04.007","url":null,"abstract":"<div><h3>Background</h3><div>As an adjunct or alternative to conventional pharmacotherapy, vagus nerve stimulation (VNS) which is FDA-approved has arisen as a novel means for various neurological disorders.</div></div><div><h3>Method</h3><div>We searched multiple databases (through 2024) for randomised trials and observational studies of VNS (invasive and transcutaneous) and pharmacological treatments (e.g. cholinergic agents, antiepileptics, antidepressants) across several neurological disorders. Prior to comparing between VNS and pharmacological treatments, subgroup analyses of VNS studies were performed for disorder type, patient demographics, VNS stimulation parameters, and treatment duration to illustrate whether VNS itself can be effective to a satisfactory extent to be compared against the conventional method. Efficacy and adverse effects were evaluated, based on the proportion of patients achieving more than 50 % symptom reduction or equivalent clinical improvement, or all-cause mortality where applicable. Evaluation between VNS and pharmacological treatments was performed through network meta-analysis, followed by assessment of heterogeneity (I<sup>2</sup>) and meta-regression. Risk of bias was evaluated with Cochrane criteria, and all studies (including those with high risk of bias) were included in the primary analysis (with sensitivity analyses excluding high-bias studies).</div></div><div><h3>Results</h3><div>We included 56 VNS-related studies (n = 5773 participants) and 29 pharmacological drug-based studies (n = 14827 participants) from spanning epilepsy, depression, migraine/headache, Alzheimer's disease, inflammatory disorders, and heart failure. A network meta-analysis directly comparing VNS to pharmacological drugs yielded an overall advantage for VNS (summary SMD = 0.27 favouring VNS, 95 % CI 0.19–0.35). However, the high heterogeneity and risk of bias have been assessed, indicating potential issues with the VNS studies.</div></div><div><h3>Conclusion</h3><div>Overall, VNS was shown to be a viable therapeutic modality across diverse neurological disorders, superior to standard pharmacological treatments with a distinct adverse effect profile. It appears particularly beneficial in conditions where conventional drugs have limited success (e.g. refractory epilepsy, depression), although patient-specific factors influence outcomes. Further high-quality trials are anticipated to optimise stimulation parameters, confirm long-term benefits, and manage patient selection for VNS.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 909-936"},"PeriodicalIF":7.6,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143865052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain StimulationPub Date : 2025-04-10DOI: 10.1016/j.brs.2025.03.021
Luke E. Osborn , Breanne Christie , David P. McMullen , Victoria Arriola , Tessy M. Thomas , Ambarish S. Pawar , Robert W. Nickl , Manuel A. Anaya , Brock A. Wester , Charles M. Greenspon , Gabriela L. Cantarero , Pablo A. Celnik , Sliman J. Bensmaia , Jeffrey M. Yau , Matthew S. Fifer , Francesco V. Tenore
{"title":"Subthreshold intracortical microstimulation of human somatosensory cortex enhances tactile sensitivity","authors":"Luke E. Osborn , Breanne Christie , David P. McMullen , Victoria Arriola , Tessy M. Thomas , Ambarish S. Pawar , Robert W. Nickl , Manuel A. Anaya , Brock A. Wester , Charles M. Greenspon , Gabriela L. Cantarero , Pablo A. Celnik , Sliman J. Bensmaia , Jeffrey M. Yau , Matthew S. Fifer , Francesco V. Tenore","doi":"10.1016/j.brs.2025.03.021","DOIUrl":"10.1016/j.brs.2025.03.021","url":null,"abstract":"<div><h3>Background</h3><div>Intracortical microstimulation (ICMS) of the somatosensory cortex activates neurons around the stimulating electrodes and can elicit tactile sensations.</div></div><div><h3>Objective</h3><div>It is not clear how the direct activation of cortical neurons influences their ability to process additional tactile inputs originating from the skin.</div></div><div><h3>Methods</h3><div>In a human implanted with chronic microelectrode arrays in both left and right somatosensory cortices, we presented mechanical vibration to the skin while simultaneously delivering ICMS and quantified the effects of combined mechanical and electrical stimulation on tactile perception.</div></div><div><h3>Results</h3><div>We found that subthreshold ICMS enhanced sensitivity to touch on the skin, as evidenced by a reduction in vibrotactile detection thresholds (median: 1.5 dB), but subthreshold vibration did not systematically impact the detectability of ICMS. Suprathreshold vibration led to an increase in ICMS thresholds (median: 2.4 dB) but suprathreshold ICMS had little impact on vibrotactile thresholds. The ICMS-induced enhancement of vibrotactile sensitivity was location dependent with the effect size decreasing as the projected field of the stimulating electrode and the locus of vibratory stimulation became farther apart.</div></div><div><h3>Conclusion</h3><div>These results demonstrate that targeted microstimulation of cortex alone can focally enhance tactile sensitivity, potentially enabling restoration or strengthening of retained tactile sensations after injury.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 900-908"},"PeriodicalIF":7.6,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143860623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Brain StimulationPub Date : 2025-04-09DOI: 10.1016/j.brs.2025.04.002
Jasmina Paneva , Teresa Schuhmann , Stefanie De Smet , Terence De Meza , Felix Duecker , Alexander T. Sack
{"title":"Affective state-dependent effects of prefrontal rTMS on the cognitive control of negative stimuli in healthy and depressed individuals","authors":"Jasmina Paneva , Teresa Schuhmann , Stefanie De Smet , Terence De Meza , Felix Duecker , Alexander T. Sack","doi":"10.1016/j.brs.2025.04.002","DOIUrl":"10.1016/j.brs.2025.04.002","url":null,"abstract":"<div><h3>Introduction</h3><div>High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) targeting the left dorsolateral prefrontal cortex (lDLPFC) is an established, clinically effective treatment for major depressive disorder (MDD). However, evidence of the cognitive effects of lDLPFC HF-rTMS, especially those cognitive functions affected by MDD, is mixed.</div></div><div><h3>Methods</h3><div>We here assessed the cognitive effects of a single, offline, 10Hz rTMS session on task performance in an emotional faces N-back (EFNBACK) task, in both healthy and depressed individuals. We measured response times, accuracy, and sensitivity, in a sham-controlled, pre-post design. Importantly, using the Beck Depression Inventory (BDI-II), we assessed whether the cognitive effects of the stimulation are state-dependent on trait-state depression.</div></div><div><h3>Results</h3><div>We found lDLPFC HF-rTMS enhanced cognitive control over angry distractors. More importantly, these cognitive control effects were state-dependent on trait-state depression. HF-rTMS produced distinct performance changes dependent on baseline BDI-II scores. As a function of BDI-II scores, we observed either increased or decreased response times on the task. Further, we observed improved accuracy and sensitivity only on angry distractor trials as BDI-II scores increased, as a consequence of lDLPFC stimulation.</div></div><div><h3>Conclusion</h3><div>These results underscore the role of HF-rTMS in enhancing executive control over negative emotional information by modulating lDLPFC, with effects varying according to depression state at the moment of the treatment session. HF-rTMS thus not only enhances inhibitory control over emotional stimuli but also exhibits such cognitive effects contingent on depressive state, contributing to our understanding of the state-dependence of therapeutic rTMS.</div></div>","PeriodicalId":9206,"journal":{"name":"Brain Stimulation","volume":"18 3","pages":"Pages 745-752"},"PeriodicalIF":7.6,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143825736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}