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  1. Article ; Online: Probing intrahemispheric interactions with a novel dual-site TMS setup.

    Hehl, Melina / Van Malderen, Shanti / Geraerts, Marc / Meesen, Raf L J / Rothwell, John C / Swinnen, Stephan P / Cuypers, Koen

    Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

    2024  Volume 158, Page(s) 180–195

    Abstract: Objective: Using dual-site transcranial magnetic stimulation (dsTMS), the effective connectivity between the primary motor cortex (M1) and adjacent brain areas such as the dorsal premotor cortex (PMd) can be investigated. However, stimulating two brain ... ...

    Abstract Objective: Using dual-site transcranial magnetic stimulation (dsTMS), the effective connectivity between the primary motor cortex (M1) and adjacent brain areas such as the dorsal premotor cortex (PMd) can be investigated. However, stimulating two brain regions in close proximity (e.g., ±2.3 cm for intrahemispheric PMd-M1) is subject to considerable spatial restrictions that potentially can be overcome by combining two standard figure-of-eight coils in a novel dsTMS setup.
    Methods: After a technical evaluation of its induced electric fields, the dsTMS setup was tested in vivo (n = 23) by applying a short-interval intracortical inhibition (SICI) protocol. Additionally, the intrahemispheric PMd-M1 interaction was probed. E-field modelling was performed using SimNIBS.
    Results: The technical evaluation yielded no major alterations of the induced electric fields due to coil overlap. In vivo, the setup reliably elicited SICI. Investigating intrahemispheric PMd-M1 interactions was feasible (inter-stimulus interval 6 ms), resulting in modulation of M1 output.
    Conclusions: The presented dsTMS setup provides a novel way to stimulate two adjacent brain regions with fewer technical and spatial limitations than previous attempts.
    Significance: This dsTMS setup enables more accurate and repeatable targeting of brain regions in close proximity and can facilitate innovation in the field of effective connectivity.
    MeSH term(s) Humans ; Evoked Potentials, Motor/physiology ; Transcranial Magnetic Stimulation/methods ; Motor Cortex/physiology ; Head
    Language English
    Publishing date 2024-01-05
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1463630-x
    ISSN 1872-8952 ; 0921-884X ; 1388-2457
    ISSN (online) 1872-8952
    ISSN 0921-884X ; 1388-2457
    DOI 10.1016/j.clinph.2023.12.128
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  2. Article ; Online: Accurate tissue segmentation from including both T1-weighted and T2-weighted MRI scans significantly affect electric field simulations of prefrontal but not motor TMS.

    Van Hoornweder, Sybren / Meesen, Raf L J / Caulfield, Kevin A

    Brain stimulation

    2022  Volume 15, Issue 4, Page(s) 942–945

    MeSH term(s) Magnetic Resonance Imaging ; Transcranial Magnetic Stimulation
    Language English
    Publishing date 2022-06-30
    Publishing country United States
    Document type Letter ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2394410-9
    ISSN 1876-4754 ; 1935-861X
    ISSN (online) 1876-4754
    ISSN 1935-861X
    DOI 10.1016/j.brs.2022.06.008
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  3. Article: Optimizing the Effect of tDCS on Motor Sequence Learning in the Elderly.

    Ghasemian-Shirvan, Ensiyeh / Ungureanu, Ruxandra / Melo, Lorena / van Dun, Kim / Kuo, Min-Fang / Nitsche, Michael A / Meesen, Raf L J

    Brain sciences

    2023  Volume 13, Issue 1

    Abstract: One of the most visible effects of aging, even in healthy, normal aging, is a decline in motor performance. The range of strategies applicable to counteract this deterioration has increased. Transcranial direct current stimulation (tDCS), a non-invasive ... ...

    Abstract One of the most visible effects of aging, even in healthy, normal aging, is a decline in motor performance. The range of strategies applicable to counteract this deterioration has increased. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique that can promote neuroplasticity, has recently gained attention. However, knowledge about optimized tDCS parameters in the elderly is limited. Therefore, in this study, we investigated the effect of different anodal tDCS intensities on motor sequence learning in the elderly. Over the course of four sessions, 25 healthy older adults (over 65 years old) completed the Serial Reaction Time Task (SRTT) while receiving 1, 2, or 3 mA of anodal or sham stimulation over the primary motor cortex (M1). Additionally, 24 h after stimulation, motor memory consolidation was assessed. The results confirmed that motor sequence learning in all tDCS conditions was maintained the following day. While increased anodal stimulation intensity over M1 showed longer lasting excitability enhancement in the elderly in a prior study, the combination of higher intensity stimulation with an implicit motor learning task showed no significant effect. Future research should focus on the reason behind this lack of effect and probe alternative stimulation protocols.
    Language English
    Publishing date 2023-01-12
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2651993-8
    ISSN 2076-3425
    ISSN 2076-3425
    DOI 10.3390/brainsci13010137
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  4. Article: A Systematic Review and Large-Scale tES and TMS Electric Field Modeling Study Reveals How Outcome Measure Selection Alters Results in a Person- and Montage-Specific Manner.

    Van Hoornweder, Sybren / Nuyts, Marten / Frieske, Joana / Verstraelen, Stefanie / Meesen, Raf L J / Caulfield, Kevin A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Background: Electric field (E-field) modeling is a potent tool to examine the cortical effects of transcranial magnetic and electrical stimulation (TMS and tES, respectively) and to address the high variability in efficacy observed in the literature. ... ...

    Abstract Background: Electric field (E-field) modeling is a potent tool to examine the cortical effects of transcranial magnetic and electrical stimulation (TMS and tES, respectively) and to address the high variability in efficacy observed in the literature. However, outcome measures used to report E-field magnitude vary considerably and have not yet been compared in detail.
    Objectives: The goal of this two-part study, encompassing a systematic review and modeling experiment, was to provide an overview of the different outcome measures used to report the magnitude of tES and TMS E-fields, and to conduct a direct comparison of these measures across different stimulation montages.
    Methods: Three electronic databases were searched for tES and/or TMS studies reporting E-field magnitude. We extracted and discussed outcome measures in studies meeting the inclusion criteria. Additionally, outcome measures were compared via models of four common tES and two TMS modalities in 100 healthy younger adults.
    Results: In the systematic review, we included 118 studies using 151 outcome measures related to E-field magnitude. Structural and spherical regions of interest (ROI) analyses and percentile-based whole-brain analyses were used most often. In the modeling analyses, we found that there was an average of only 6% overlap between ROI and percentile-based whole-brain analyses in the investigated volumes within the same person. The overlap between ROI and whole-brain percentiles was montage- and person-specific, with more focal montages such as 4Ã-1 and APPS-tES, and figure-of-eight TMS showing up to 73%, 60%, and 52% overlap between ROI and percentile approaches respectively. However, even in these cases, 27% or more of the analyzed volume still differed between outcome measures in every analyses.
    Conclusions: The choice of outcome measures meaningfully alters the interpretation of tES and TMS E-field models. Well-considered outcome measure selection is imperative for accurate interpretation of results, valid between-study comparisons, and depends on stimulation focality and study goals. We formulated four recommendations to increase the quality and rigor of E-field modeling outcome measures. With these data and recommendations, we hope to guide future studies towards informed outcome measure selection, and improve the comparability of studies.
    Language English
    Publishing date 2023-02-22
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.02.22.529540
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  5. Article ; Online: Outcome measures for electric field modeling in tES and TMS: A systematic review and large-scale modeling study.

    Van Hoornweder, Sybren / Nuyts, Marten / Frieske, Joana / Verstraelen, Stefanie / Meesen, Raf L J / Caulfield, Kevin A

    NeuroImage

    2023  Volume 281, Page(s) 120379

    Abstract: Background: Electric field (E-field) modeling is a potent tool to estimate the amount of transcranial magnetic and electrical stimulation (TMS and tES, respectively) that reaches the cortex and to address the variable behavioral effects observed in the ... ...

    Abstract Background: Electric field (E-field) modeling is a potent tool to estimate the amount of transcranial magnetic and electrical stimulation (TMS and tES, respectively) that reaches the cortex and to address the variable behavioral effects observed in the field. However, outcome measures used to quantify E-fields vary considerably and a thorough comparison is missing.
    Objectives: This two-part study aimed to examine the different outcome measures used to report on tES and TMS induced E-fields, including volume- and surface-level gray matter, region of interest (ROI), whole brain, geometrical, structural, and percentile-based approaches. The study aimed to guide future research in informed selection of appropriate outcome measures.
    Methods: Three electronic databases were searched for tES and/or TMS studies quantifying E-fields. The identified outcome measures were compared across volume- and surface-level E-field data in ten tES and TMS modalities targeting two common targets in 100 healthy individuals.
    Results: In the systematic review, we extracted 308 outcome measures from 202 studies that adopted either a gray matter volume-level (n = 197) or surface-level (n = 111) approach. Volume-level results focused on E-field magnitude, while surface-level data encompassed E-field magnitude (n = 64) and normal/tangential E-field components (n = 47). E-fields were extracted in ROIs, such as brain structures and shapes (spheres, hexahedra and cylinders), or the whole brain. Percentiles or mean values were mostly used to quantify E-fields. Our modeling study, which involved 1,000 E-field models and > 1,000,000 extracted E-field values, revealed that different outcome measures yielded distinct E-field values, analyzed different brain regions, and did not always exhibit strong correlations in the same within-subject E-field model.
    Conclusions: Outcome measure selection significantly impacts the locations and intensities of extracted E-field data in both tES and TMS E-field models. The suitability of different outcome measures depends on the target region, TMS/tES modality, individual anatomy, the analyzed E-field component and the research question. To enhance the quality, rigor, and reproducibility in the E-field modeling domain, we suggest standard reporting practices across studies and provide four recommendations.
    MeSH term(s) Humans ; Reproducibility of Results ; Brain/physiology ; Cerebral Cortex ; Electricity ; Gray Matter ; Transcranial Magnetic Stimulation/methods ; Transcranial Direct Current Stimulation/methods
    Language English
    Publishing date 2023-09-15
    Publishing country United States
    Document type Systematic Review ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 1147767-2
    ISSN 1095-9572 ; 1053-8119
    ISSN (online) 1095-9572
    ISSN 1053-8119
    DOI 10.1016/j.neuroimage.2023.120379
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  6. Article ; Online: Age-dependent non-linear neuroplastic effects of cathodal tDCS in the elderly population: a titration study.

    Ghasemian-Shirvan, Ensiyeh / Mosayebi-Samani, Mohsen / Farnad, Leila / Kuo, Min-Fang / Meesen, Raf L J / Nitsche, Michael A

    Brain stimulation

    2022  Volume 15, Issue 2, Page(s) 296–305

    Abstract: Background: Neuromodulatory effects of transcranial direct current stimulation (tDCS) in older humans have shown heterogeneous results, possibly due to sub-optimal stimulation protocols associated with limited knowledge about optimized stimulation ... ...

    Abstract Background: Neuromodulatory effects of transcranial direct current stimulation (tDCS) in older humans have shown heterogeneous results, possibly due to sub-optimal stimulation protocols associated with limited knowledge about optimized stimulation parameters in this age group. We systematically explored the association between the stimulation dosage of cathodal tDCS and induced after-effects on motor cortex excitability in the elderly.
    Method: Thirty-nine healthy volunteers in two age groups, namely Pre-Elderly (50-65 years) and Elderly (66-80 years), participated in the study. Ten sessions of cathodal tDCS, with a combination of four intensities (1, 2, 3 mA and sham) and three durations (15, 20, 30 min) were conducted over the M1 in each participant. Cortical excitability changes were monitored with TMS-induced motor evoked potentials (MEPs) for up to 2 h after stimulation.
    Results: Motor cortex excitability was reduced by cathodal stimulation intensities of 1 and 3 mA in both age groups, in accordance with results observed in the younger age groups of previous studies. For the 2 mA stimulation condition, an age-dependent conversion of plasticity into a stimulation duration-dependent excitability enhancement was observed in the Pre-Elderly group, whereas in the Elderly group, LTD-like plasticity was preserved, or abolished, depending on stimulation duration.
    Conclusion: The LTD-like plasticity effects induced by cathodal tDCS originally described in young adults are also observable in older humans, but non-linearities of the resulting plasticity were partially preserved only in the Pre-Elderly, but not the Elderly group. These results aid in understanding age-dependent plasticity dynamics in humans, and to define more efficient tDCS protocols in the aging brain.
    MeSH term(s) Aged ; Cortical Excitability/physiology ; Evoked Potentials, Motor/physiology ; Humans ; Middle Aged ; Motor Cortex/physiology ; Neuronal Plasticity/physiology ; Transcranial Direct Current Stimulation/methods ; Transcranial Magnetic Stimulation/methods ; Young Adult
    Language English
    Publishing date 2022-01-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2394410-9
    ISSN 1876-4754 ; 1935-861X
    ISSN (online) 1876-4754
    ISSN 1935-861X
    DOI 10.1016/j.brs.2022.01.011
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  7. Article: Addressing transcranial electrical stimulation variability through prospective individualized dosing of electric field strength in 300 participants across two samples

    Van Hoornweder, Sybren / Caulfield, Kevin A. / Nitsche, Michael / Thielscher, Axel / Meesen, Raf L. J.

    Journal of Neural Engineering

    The 2-SPED approach

    2022  Volume 19, Issue 5, Page(s) No

    Abstract: Objective: Transcranial electrical stimulation (tES) is a promising method for modulating brain activity and excitability with variable results to date. To minimize electric (E-)field strength variability, we introduce the 2-sample prospective E-field ... ...

    Title translation Behandlung der Variabilität der transkraniellen elektrischen Stimulation durch prospektive individualisierte Dosierung der elektrischen Feldstärke bei 300 Teilnehmern in zwei Stichproben: Der 2-SPED-Ansatz. (DeepL)
    Abstract Objective: Transcranial electrical stimulation (tES) is a promising method for modulating brain activity and excitability with variable results to date. To minimize electric (E-)field strength variability, we introduce the 2-sample prospective E-field dosing (2-SPED) approach, which uses E-field strengths induced by tES in a first population to individualize stimulation intensity in a second population. Approach: We performed E-field modeling of three common tES montages in 300 healthy younger adults. First, permutation analyses identified the sample size required to obtain a stable group average E-field in the primary motor cortex (M1), with stability being defined as the number of participants where all group-average E-field strengths +/- standard deviation did not leave the population's 5-95 percentile range. Second, this stable group average was used to individualize tES intensity in a second independent population (n = 100). The impact of individualized versus fixed intensity tES on E-field strength variability was analyzed. Main results: In the first population, stable group average E-field strengths (V/m) in M1 were achieved at 74-85 participants, depending on the tES montage. Individualizing the stimulation intensity (mA) in the second population resulted in uniform M1 E-field strength (all p < 0.001) and significantly diminished peak cortical E-field strength variability (all p < 0.01), across all montages. Significance: 2-SPED is a feasible way to prospectively induce more uniform E-field strengths in a region of interest. Future studies might apply 2-SPED to investigate whether decreased E-field strength variability also results in decreased physiological and behavioral variability in response to tES.
    Keywords Brain ; Electrical Brain Stimulation ; Electrical Stimulation ; Elektrische Hirnstimulation ; Elektrische Stimulation ; Gehirn ; Transcranial Direct Current Stimulation ; Transkranielle Gleichstromstimulation
    Language English
    Document type Article
    ZDB-ID 2170901-4
    ISSN 1741-2552 ; 1741-2560
    ISSN (online) 1741-2552
    ISSN 1741-2560
    DOI 10.1088/1741-2552/ac9a78
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  8. Article: Optimizing the effect of tDCS on motor sequence learning in the elderly

    Ghasemian-Shirvan, Ensiyeh / Ungureanu, Ruxandra / Melo, Lorena / van Dun, Kim / Kuo, Min-Fang / Nitsche, Michael A. / Meesen, Raf L. J.

    Brain Sciences

    2023  Volume 13, Issue 1, Page(s) No

    Abstract: One of the most visible effects of aging, even in healthy, normal aging, is a decline in motor performance. The range of strategies applicable to counteract this deterioration has increased. Transcranial direct current stimulation (tDCS), a non-invasive ... ...

    Title translation Optimierung der Wirkung von tDCS auf das Erlernen motorischer Abläufe bei älteren Menschen (DeepL)
    Abstract One of the most visible effects of aging, even in healthy, normal aging, is a decline in motor performance. The range of strategies applicable to counteract this deterioration has increased. Transcranial direct current stimulation (tDCS), a non-invasive brain stimulation technique that can promote neuroplasticity, has recently gained attention. However, knowledge about optimized tDCS parameters in the elderly is limited. Therefore, in this study, we investigated the effect of different anodal tDCS intensities on motor sequence learning in the elderly. Over the course of four sessions, 25 healthy older adults (over 65 years old) completed the Serial Reaction Time Task (SRTT) while receiving 1, 2, or 3 mA of anodal or sham stimulation over the primary motor cortex (M1). Additionally, 24 h after stimulation, motor memory consolidation was assessed. The results confirmed that motor sequence learning in all tDCS conditions was maintained the following day. While increased anodal stimulation intensity over M1 showed longer lasting excitability enhancement in the elderly in a prior study, the combination of higher intensity stimulation with an implicit motor learning task showed no significant effect. Future research should focus on the reason behind this lack of effect and probe alternative stimulation protocols.
    Keywords Aging ; Altern ; Electrical Brain Stimulation ; Elektrische Hirnstimulation ; Gedächtniskonsolidierung ; Höheres Erwachsenenalter ; Memory Consolidation ; Motor Cortex ; Motorischer Kortex ; Neural Plasticity ; Neuronale Plastizität ; Older Adulthood ; Perceptual Motor Learning ; Sensumotorisches Lernen ; Sequential Learning ; Sequenzielles Lernen ; Transcranial Direct Current Stimulation ; Transkranielle Gleichstromstimulation
    Language English
    Document type Article
    DOI 10.3390/brainsci13010137
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  9. Article: Age-dependent non-linear neuroplastic effects of cathodal tDCS in the elderly population

    Ghasemian-Shirvan, Ensiyeh / Mosayebi-Samani, Mohsen / Farnad, Leila / Kuo, Min-Fang / Meesen, Raf L. J. / Nitsche, Michael A.

    Brain Stimulation

    A titration study

    2022  Volume 15, Issue 2, Page(s) 296–305

    Abstract: Background: Neuromodulatory effects of transcranial direct current stimulation (tDCS) in older humans have shown heterogeneous results, possibly due to sub-optimal stimulation protocols associated with limited knowledge about optimized stimulation ... ...

    Title translation Altersabhängige nichtlineare neuroplastische Effekte der kathodalen tDCS bei älteren Menschen: Eine Titrationsstudie
    Abstract Background: Neuromodulatory effects of transcranial direct current stimulation (tDCS) in older humans have shown heterogeneous results, possibly due to sub-optimal stimulation protocols associated with limited knowledge about optimized stimulation parameters in this age group. We systematically explored the association between the stimulation dosage of cathodal tDCS and induced after-effects on motor cortex excitability in the elderly. Method: Thirty-nine healthy volunteers in two age groups, namely Pre-Elderly (50-65 years) and Elderly (66-80 years), participated in the study. Ten sessions of cathodal tDCS, with a combination of four intensities (1, 2, 3 mA and sham) and three durations (15, 20, 30 min) were conducted over the M1 in each participant. Cortical excitability changes were monitored with TMS-induced motor evoked potentials (MEPs) for up to 2 h after stimulation. Results: Motor cortex excitability was reduced by cathodal stimulation intensities of 1 and 3 mA in both age groups, in accordance with results observed in the younger age groups of previous studies. For the 2 mA stimulation condition, an age-dependent conversion of plasticity into a stimulation duration-dependent excitability enhancement was observed in the Pre-Elderly group, whereas in the Elderly group, LTD-like plasticity was preserved, or abolished, depending on stimulation duration. Conclusion: The LTD-like plasticity effects induced by cathodal tDCS originally described in young adults are also observable in older humans, but non-linearities of the resulting plasticity were partially preserved only in the Pre-Elderly, but not the Elderly group. These results aid in understanding age-dependent plasticity dynamics in humans, and to define more efficient tDCS protocols in the aging brain.
    Keywords Age Differences ; Aging ; Altern ; Altersunterschiede ; Höheres Erwachsenenalter ; Motor Cortex ; Motorischer Kortex ; Neural Plasticity ; Neuronale Plastizität ; Older Adulthood ; Somatosensorisch evozierte Potenziale ; Somatosensory Evoked Potentials ; Transcranial Direct Current Stimulation ; Transcranial Magnetic Stimulation ; Transkranielle Gleichstromstimulation ; Transkranielle Magnetstimulation
    Language English
    Document type Article
    ZDB-ID 2394410-9
    ISSN 1935-861X
    ISSN 1935-861X
    DOI 10.1016/j.brs.2022.01.011
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  10. Article: Induced Suppression of the Left Dorsolateral Prefrontal Cortex Favorably Changes Interhemispheric Communication During Bimanual Coordination in Older Adults-A Neuronavigated rTMS Study.

    Verstraelen, Stefanie / van Dun, Kim / Duque, Julie / Fujiyama, Hakuei / Levin, Oron / Swinnen, Stephan P / Cuypers, Koen / Meesen, Raf L J

    Frontiers in aging neuroscience

    2020  Volume 12, Page(s) 149

    Abstract: Recent transcranial magnetic stimulation (TMS) research indicated that the ability of the dorsolateral prefrontal cortex (DLPFC) to disinhibit the contralateral primary motor cortex (M1) during motor preparation is an important predictor for bimanual ... ...

    Abstract Recent transcranial magnetic stimulation (TMS) research indicated that the ability of the dorsolateral prefrontal cortex (DLPFC) to disinhibit the contralateral primary motor cortex (M1) during motor preparation is an important predictor for bimanual motor performance in both young and older healthy adults. However, this DLPFC-M1 disinhibition is reduced in older adults. Here, we transiently suppressed left DLPFC using repetitive TMS (rTMS) during a cyclical bimanual task and investigated the effect of left DLPFC suppression: (1) on the projection from left DLPFC to the contralateral M1; and (2) on motor performance in 21 young (mean age ± SD = 21.57 ± 1.83) and 20 older (mean age ± SD = 69.05 ± 4.48) healthy adults. As predicted, without rTMS, older adults showed compromised DLPFC-M1 disinhibition as compared to younger adults and less preparatory DLPFC-M1 disinhibition was related to less accurate performance, irrespective of age. Notably, rTMS-induced DLPFC suppression restored DLPFC-M1 disinhibition in older adults and improved performance accuracy right after the local suppression in both age groups. However, the rTMS-induced gain in disinhibition was not correlated with the gain in performance. In sum, this novel rTMS approach advanced our mechanistic understanding of how left DLPFC regulates right M1 and allowed us to establish the causal role of left DLPFC in bimanual coordination.
    Language English
    Publishing date 2020-05-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2558898-9
    ISSN 1663-4365
    ISSN 1663-4365
    DOI 10.3389/fnagi.2020.00149
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