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  • 1
    Online Resource
    Online Resource
    Blood-brain barrier opening with focused ultrasound in Parkinson’s disease dementia
    Springer Science and Business Media LLC ; 2021
    In:  Nature Communications Vol. 12, No. 1 ( 2021-02-03)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-02-03)
    Abstract: MR-guided focused ultrasound (MRgFUS), in combination with intravenous microbubble administration, has been applied for focal temporary BBB opening in patients with neurodegenerative disorders and brain tumors. MRgFUS could become a therapeutic tool for drug delivery of putative neurorestorative therapies. Treatment for Parkinson’s disease with dementia (PDD) is an important unmet need. We initiated a prospective, single-arm, non-randomized, proof-of-concept, safety and feasibility phase I clinical trial (NCT03608553), which is still in progress. The primary outcomes of the study were to demonstrate the safety, feasibility and reversibility of BBB disruption in PDD, targeting the right parieto-occipito-temporal cortex where cortical pathology is foremost in this clinical state. Changes in β-amyloid burden, brain metabolism after treatments and neuropsychological assessments, were analyzed as exploratory measurements. Five patients were recruited from October 2018 until May 2019, and received two treatment sessions separated by 2–3 weeks. The results are set out in a descriptive manner. Overall, this procedure was feasible and reversible with no serious clinical or radiological side effects. We report BBB opening in the parieto-occipito-temporal junction in 8/10 treatments in 5 patients as demonstrated by gadolinium enhancement. In all cases the procedures were uneventful and no side effects were encountered associated with BBB opening. From pre- to post-treatment, mild cognitive improvement was observed, and no major changes were detected in amyloid or fluorodeoxyglucose PET. MRgFUS-BBB opening in PDD is thus safe, reversible, and can be performed repeatedly. This study provides encouragement for the concept of BBB opening for drug delivery to treat dementia in PD and other neurodegenerative disorders.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-021-21022-9
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2553671-0
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  • 2
    Online Resource
    Online Resource
    Focused ultrasound subthalamotomy in patients with asymmetric Parkinson's disease: a pilot study
    Elsevier BV ; 2018
    In:  The Lancet Neurology Vol. 17, No. 1 ( 2018-01), p. 54-63
    Details
    In: The Lancet Neurology, Elsevier BV, Vol. 17, No. 1 ( 2018-01), p. 54-63
    Type of Medium: Online Resource
    ISSN: 1474-4422
    URL: Article
    DOI: 10.1016/S1474-4422(17)30403-9
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2018
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  • 3
    Online Resource
    Online Resource
    Striatal Blood–Brain Barrier Opening in Parkinson's Disease Dementia: A Pilot Exploratory Study
    Wiley ; 2022
    In:  Movement Disorders Vol. 37, No. 10 ( 2022-10), p. 2057-2065
    Details
    In: Movement Disorders, Wiley, Vol. 37, No. 10 ( 2022-10), p. 2057-2065
    Abstract: Parkinson's disease (PD) exhibits a high prevalence of dementia as disease severity and duration progress. Focused ultrasound (FUS) has been applied for transient blood–brain barrier (BBB) opening of cortical regions in neurodegenerative disorders. The striatum is a primary target for delivery of putative therapeutic agents in PD. Objective Here, we report a prospective, single‐arm, nonrandomized, proof‐of‐concept, phase I clinical trial (NCT03608553 amended) in PD with dementia to test the safety and feasibility of striatal BBB opening in PD patients. Methods Seven PD patients with cognitive impairment were treated for BBB opening in the posterior putamen. This was performed in two sessions separated by 2 to 4 weeks, where the second session included bilateral putamina opening in 3 patients. Primary outcome measures included safety and feasibility of focal striatal BBB opening. Changes in motor and cognitive functions, magnetic resonance imaging (MRI), 18 F‐fluorodopa (FDOPA), and β‐amyloid PET (positron emission tomography) images were determined. Results The procedure was feasible and well tolerated, with no serious adverse events. No neurologically relevant change in motor and cognitive (battery of neuropsychological tests) functions was recognized at follow‐up. MRI revealed putamen BBB closing shortly after treatment (24 hours to 14 days) and ruled out hemorrhagic and ischemic lesions. There was a discrete but significant reduction in β‐amyloid uptake in the targeted region and no change in FDOPA PET. Conclusions These initial results indicate that FUS‐mediated striatal BBB opening is feasible and safe and therefore could become an effective tool to facilitate the delivery of putative neurorestorative molecules in PD. © 2022 International Parkinson and Movement Disorder Society.
    Type of Medium: Online Resource
    ISSN: 0885-3185 , 1531-8257
    URL: Issue
    URL: Article
    DOI: 10.1002/mds.v37.10
    DOI: 10.1002/mds.29134
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2041249-6
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  • 4
    Online Resource
    Online Resource
    Static magnetic field stimulation of the supplementary motor area modulates resting-state activity and motor behavior
    Springer Science and Business Media LLC ; 2019
    In:  Communications Biology Vol. 2, No. 1 ( 2019-10-31)
    Details
    In: Communications Biology, Springer Science and Business Media LLC, Vol. 2, No. 1 ( 2019-10-31)
    Abstract: Focal application of a strong static magnetic field over the human scalp induces measurable local changes in brain function. Whether it also induces distant effects across the brain and how these local and distant effects collectively affect motor behavior remains unclear. Here we applied transcranial static magnetic field stimulation (tSMS) over the supplementary motor area (SMA) in healthy subjects. At a behavioral level, tSMS increased the time to initiate movement while decreasing errors in choice reaction-time tasks. At a functional level, tSMS increased SMA resting-state fMRI activity and bilateral functional connectivity between the SMA and both the paracentral lobule and the lateral frontotemporal cortex, including the inferior frontal gyrus. These results suggest that tSMS over the SMA can induce behavioral aftereffects associated with modulation of both local and distant functionally-connected cortical circuits involved in the control of speed-accuracy tradeoffs, thus offering a promising protocol for cognitive and clinical research.
    Type of Medium: Online Resource
    ISSN: 2399-3642
    URL: Article
    DOI: 10.1038/s42003-019-0643-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2019
    detail.hit.zdb_id: 2919698-X
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  • 5
    Online Resource
    Online Resource
    Noninvasive modulation of human corticostriatal activity
    Proceedings of the National Academy of Sciences ; 2023
    In:  Proceedings of the National Academy of Sciences Vol. 120, No. 15 ( 2023-04-11)
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 120, No. 15 ( 2023-04-11)
    Abstract: Corticostriatal activity is an appealing target for nonpharmacological treatments of brain disorders. In humans, corticostriatal activity may be modulated with noninvasive brain stimulation (NIBS). However, a NIBS protocol with a sound neuroimaging measure demonstrating a change in corticostriatal activity is currently lacking. Here, we combine transcranial static magnetic field stimulation (tSMS) with resting-state functional MRI (fMRI). We first present and validate the ISAAC analysis, a well-principled framework that disambiguates functional connectivity between regions from local activity within regions. All measures of the framework suggested that the region along the medial cortex displaying greater functional connectivity with the striatum is the supplementary motor area (SMA), where we applied tSMS. We then use a data-driven version of the framework to show that tSMS of the SMA modulates the local activity in the SMA proper, in the adjacent sensorimotor cortex, and in the motor striatum. We finally use a model-driven version of the framework to clarify that the tSMS-induced modulation of striatal activity can be primarily explained by a change in the shared activity between the modulated motor cortical areas and the motor striatum. These results suggest that corticostriatal activity can be targeted, monitored, and modulated noninvasively in humans.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.2219693120
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2023
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 6
    Online Resource
    Online Resource
    The Supplementary Motor Area and Automatic Cognitive Control: Lack of Evidence from Two Neuromodulation Techniques
    MIT Press ; 2023
    In:  Journal of Cognitive Neuroscience Vol. 35, No. 3 ( 2023-03-01), p. 439-451
    Details
    In: Journal of Cognitive Neuroscience, MIT Press, Vol. 35, No. 3 ( 2023-03-01), p. 439-451
    Abstract: The SMA is fundamental in planning voluntary movements and execution of some cognitive control operations. Specifically, the SMA has been known to play a dominant role in controlling goal-directed actions as well as those that are highly predicted (i.e., automatic). Yet, the essential contribution of SMA in goal-directed or automatic control of behavior is scarce. Our objective was to test the possible direct role of SMA in automatic and voluntary response inhibition. We separately applied two noninvasive brain stimulation (NIBS) inhibitory techniques over SMA: either continuous theta-burst stimulation using repetitive transcranial magnetic stimulation or transcranial static magnetic field stimulation. Each NIBS technique was performed in a randomized, crossover, sham-controlled design. Before applying NIBS, participants practiced a go/no-go learning task where associations between stimulus and stopping behaviors were created (initiation and inhibition). After applying each NIBS, participants performed a go/no-go task with reversed associations (automatic control) and the stop signal task (voluntary control). Learning associations between stimuli and response initiation/inhibition was achieved by participants and therefore automatized during training. However, no significant differences between real and sham NIBS were found in either automatic (go/no-go learning task) or voluntary inhibition (stop signal task), with Bayesian statistics providing moderate evidence of absence. In conclusion, our results are compatible with a nondirect involvement of SMA in automatic control of behavior. Further studies are needed to prove a noncausal link between prior neuroimaging findings relative to SMA controlling functions and the observed behavior.
    Type of Medium: Online Resource
    ISSN: 0898-929X , 1530-8898
    URL: Article
    DOI: 10.1162/jocn_a_01954
    Language: English
    Publisher: MIT Press
    Publication Date: 2023
    SSG: 5,2
    SSG: 7,11
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