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Blomstedt, Patric
Publications (10 of 120) Show all publications
Awad, A., Grill, F., Blomstedt, P., Nyberg, L. & Eriksson, J. (2024). Deep brain stimulation does not modulate resting-state functional connectivity in essential tremor. Brain Communications, 6(2), Article ID fcae012.
Open this publication in new window or tab >>Deep brain stimulation does not modulate resting-state functional connectivity in essential tremor
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2024 (English)In: Brain Communications, E-ISSN 2632-1297, Vol. 6, no 2, article id fcae012Article in journal (Refereed) Published
Abstract [en]

While the effectiveness of deep brain stimulation in alleviating essential tremor is well-established, the underlying mechanisms of the treatment are unclear. Essential tremor, as characterized by tremor during action, is proposed to be driven by a dysfunction in the cerebello-thalamo-cerebral circuit that is evident not only during motor actions but also during rest. Stimulation effects on resting-state functional connectivity were investigated by functional MRI in 16 essential tremor patients with fully implanted deep brain stimulation in the caudal zona incerta during On-and-Off therapeutic stimulation, in a counterbalanced design. Functional connectivity was calculated between different constellations of sensorimotor as well as non-sensorimotor regions (as derived from seed-based and data-driven approaches), and compared between On and Off stimulation. We found that deep brain stimulation did not modulate resting-state functional connectivity. The lack of modulation by deep brain stimulation during resting-state, in combination with previously demonstrated effects on the cerebello-thalamo-cerebral circuit during motor tasks, suggests an action-dependent modulation of the stimulation in essential tremor.

Place, publisher, year, edition, pages
Oxford University Press, 2024
Keywords
caudal zona incerta, deep brain stimulation, essential tremor, functional connectivity, resting-state fMRI
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-222642 (URN)10.1093/braincomms/fcae012 (DOI)001184993600003 ()38482375 (PubMedID)2-s2.0-85188020052 (Scopus ID)
Funder
Knut and Alice Wallenberg FoundationRegion Västerbotten
Available from: 2024-04-19 Created: 2024-04-19 Last updated: 2024-04-19Bibliographically approved
Slavin, K. V., Régis, J. M., Hodaie, M., Doshi, P. K., Blomstedt, P. & Chang, J. W. (2024). Letter: functional neurosurgery - a neglected aspect of global neurosurgery: call to action [Letter to the editor]. Neurosurgery, 94(4), e55-e56
Open this publication in new window or tab >>Letter: functional neurosurgery - a neglected aspect of global neurosurgery: call to action
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2024 (English)In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 94, no 4, p. e55-e56Article in journal, Letter (Other academic) Published
Place, publisher, year, edition, pages
Wolters Kluwer, 2024
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-222656 (URN)10.1227/neu.0000000000002850 (DOI)38265211 (PubMedID)2-s2.0-85188202214 (Scopus ID)
Available from: 2024-04-19 Created: 2024-04-19 Last updated: 2024-04-19Bibliographically approved
Blomstedt, Y., Stenmark Persson, R., Awad, A., Hariz, G.-M., Philipson, J., Hariz, M., . . . Blomstedt, P. (2023). 10 years follow-up of deep brain stimulation in the caudal zona incerta/posterior subthalamic area for essential tremor. Movement Disorders Clinical Practice, 10(5), 783-793
Open this publication in new window or tab >>10 years follow-up of deep brain stimulation in the caudal zona incerta/posterior subthalamic area for essential tremor
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2023 (English)In: Movement Disorders Clinical Practice, E-ISSN 2330-1619, Vol. 10, no 5, p. 783-793Article in journal (Refereed) Published
Abstract [en]

Background: Long-term data on the effects of deep brain stimulation (DBS) for essential tremor (ET) is scarce, especially regarding DBS in the caudal Zona incerta (cZi) and the posterior subthalamic area (PSA). Objectives: The aim of this prospective study was to evaluate the effect of cZi/PSA DBS in ET at 10 years after surgery.

Methods: Thirty-four patients were included. All patients received cZi/PSA DBS (5 bilateral/29 unilateral) and were evaluated at regular intervals using the essential tremor rating scale (ETRS).

Results: One year after surgery, there was a 66.4% improvement of total ETRS and 70.7% improvement of tremor (items 1–9) compared with the preoperative baseline. Ten years after surgery, 14 patients had died and 3 were lost to follow-up. In the remaining 17 patients, a significant improvement was maintained (50.8% for total ETRS and 55.8% for tremor items). On the treated side the scores of hand function (items 11–14) had improved by 82.6% at 1 year after surgery, and by 66.1% after 10 years. Since off-stimulation scores did not differ between year 1 and 10, this 20% deterioration of on-DBS scores was interpreted as a habituation. There was no significant increase in stimulation parameters beyond the first year.

Conclusions: This 10 year follow up study, found cZi/PSA DBS for ET to be a safe procedure with a mostly retained effect on tremor, compared to 1 year after surgery, and in the absence of increase in stimulation parameters. The modest deterioration of effect of DBS on tremor was interpreted as habituation.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
DBS, essential tremor, long-term follow-up, posterior subthalamic area, zona incerta
National Category
Neurology Surgery
Identifiers
urn:nbn:se:umu:diva-206764 (URN)10.1002/mdc3.13729 (DOI)000961376000001 ()2-s2.0-85151937204 (Scopus ID)
Funder
Swedish Research Council, 2018-00618
Available from: 2023-04-28 Created: 2023-04-28 Last updated: 2023-11-13Bibliographically approved
Schulder, M., Mishra, A., Mammis, A., Horn, A., Boutet, A., Blomstedt, P., . . . Chang, J. W. (2023). Advances in technical aspects of deep brain stimulation surgery. Stereotactic and Functional Neurosurgery, 101(2), 112-134
Open this publication in new window or tab >>Advances in technical aspects of deep brain stimulation surgery
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2023 (English)In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 101, no 2, p. 112-134Article, review/survey (Refereed) Published
Abstract [en]

Background: Deep brain stimulation has become an established technology for the treatment of patients with a wide variety of conditions, including movement disorders, psychiatric disorders, epilepsy, and pain. Surgery for implantation of DBS devices has enhanced our understanding of human physiology, which in turn has led to advances in DBS technology. Our group has previously published on these advances, proposed future developments, and examined evolving indications for DBS.

Summary: The crucial roles of structural MR imaging pre-, intra-, and post-DBS procedure in target visualization and confirmation of targeting are described, with discussion of new MR sequences and higher field strength MRI enabling direct visualization of brain targets. The incorporation of functional and connectivity imaging in procedural workup and their contribution to anatomical modelling is reviewed. Various tools for targeting and implanting electrodes, including frame-based, frameless, and robot-assisted, are surveyed, and their pros and cons are described. Updates on brain atlases and various software used for planning target coordinates and trajectories are presented. The pros and cons of asleep versus awake surgery are discussed. The role and value of microelectrode recording and local field potentials are described, as well as the role of intraoperative stimulation. Technical aspects of novel electrode designs and implantable pulse generators are presented and compared.

Place, publisher, year, edition, pages
S. Karger, 2023
Keywords
Deep brain stimulation, Neuroimaging, Review, Surgical technique
National Category
Neurosciences Neurology
Identifiers
urn:nbn:se:umu:diva-205741 (URN)10.1159/000529040 (DOI)000940265300001 ()36809747 (PubMedID)2-s2.0-85149267013 (Scopus ID)
Available from: 2023-03-16 Created: 2023-03-16 Last updated: 2023-06-19Bibliographically approved
Hariz, M., Blomstedt, Y., Blomstedt, P. & Hariz, G.-M. (2023). Anthropology of deep brain stimulation; the 30th anniversary of STN DBS in 2023. Movement Disorders Clinical Practice, 10(9), 1285-1292
Open this publication in new window or tab >>Anthropology of deep brain stimulation; the 30th anniversary of STN DBS in 2023
2023 (English)In: Movement Disorders Clinical Practice, E-ISSN 2330-1619, Vol. 10, no 9, p. 1285-1292Article, review/survey (Refereed) Published
Abstract [en]

Background: The year 2023 marks the 30th anniversary of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson’s disease (PD). This procedure prompted a universal interest in DBS for various brain disorders and resulted in a unique expansion of clinical and scientific collaboration between many disciplines, with impact on many aspects of society.

Objective: To study the anthropology of DBS, that is, its ethno-geographic origins, its evolution, its impact on clinicians and scientists, and its influence on society at large.

Material and Methods: The authors scrutinized the geo-ethnic origins of the pioneers of modern DBS, and they evaluated, based on the literature and on a long-term praxis, the development of DBS and its impact on clinicians, on healthcare, and on society.

Results: Scientists and clinicians from various geo-ethnic origins pioneered modern DBS, leading to worldwide spread of this procedure and to the establishment of large multidisciplinary teams in many centers. Neurologists became actively involved in surgery and took on new laborious tasks of programming ever more complicated DBS systems. Publications sky-rocketed and the global spread of DBS impacted positively on several aspects of society, including healthcare, awareness of neurological diseases, interdisciplinary relations, conferences, patient organizations, unemployment, industry, etc.

Conclusions: STN DBS has boosted the field of deep brain electrotherapy for many neurological and psychiatric illnesses, and DBS has generated a global benefit on many aspects of society, well beyond its clinical benefits on symptoms of diseases. With the ever-increasing indications for DBS, more positive global impact is expected.

Place, publisher, year, edition, pages
John Wiley & Sons, 2023
Keywords
anthropology, deep brain stimulation, movement disorders, Parkinson's disease, subthalamic nucleus
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-214291 (URN)10.1002/mdc3.13858 (DOI)001065271200001 ()37772285 (PubMedID)2-s2.0-85169423554 (Scopus ID)
Available from: 2023-09-11 Created: 2023-09-11 Last updated: 2023-12-19Bibliographically approved
Philipson, J., Naesström, M., Johansson, J. D., Hariz, M., Blomstedt, P. & Jahanshahi, M. (2023). Deep brain stimulation in the ALIC-BNST region targeting the bed nucleus of stria terminalis in patients with obsessive–compulsive disorder: effects on cognition after 12 months. Acta Neurochirurgica, 165(5), 1201-1214
Open this publication in new window or tab >>Deep brain stimulation in the ALIC-BNST region targeting the bed nucleus of stria terminalis in patients with obsessive–compulsive disorder: effects on cognition after 12 months
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2023 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 165, no 5, p. 1201-1214Article in journal (Refereed) Published
Abstract [en]

Purpose: The aim of this study was to evaluate cognitive effects 12 months after Deep Brain Stimulation (DBS) of the Bed Nucleus of Stria Terminalis (BNST) in patients with refractory Obsessive–Compulsive Disorder (OCD).

Methods: Eight patients (5 female; mean ± SD age 36 ± 15) with OCD were included. A neuropsychological test battery covering verbal and spatial episodic memory, executive function, and attention was administered preoperatively and 12 months after surgery. Medical records were used as a source for descriptive data to probe for any changes not covered by standardized checklists and the Yale-Brown Obsessive Compulsive Scale (Y-BOCS), the primary outcome measure.

Results: At 12 months, seven patients showed response to DBS: three were full responders (i.e., Y-BOCS ≥ 35% improvement), and four were partial responders (Y-BOCS 25–34% improvement). Relative to baseline, there was a slight decline on visuo-spatial learning (p = 0.027), and improved performance on the Color-Word Interference inhibition/switching subtest (p = 0.041), suggesting improvement in cognitive flexibility.

Conclusions: DBS in the BNST for treatment refractory OCD generates very few adverse cognitive effects and improves cognitive flexibility after 12 months of stimulation. The improvement in Y-BOCS and the absence of major cognitive side effects support the BNST as a potential target for DBS in severe OCD.

Place, publisher, year, edition, pages
Springer, 2023
Keywords
Bed nucleus of stria terminalis, BNST, Cognition, Deep brain stimulation, DBS, Obsessive–compulsive disorder, OCD
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-199475 (URN)10.1007/s00701-022-05351-2 (DOI)000849141100001 ()36056244 (PubMedID)2-s2.0-85137480737 (Scopus ID)
Available from: 2022-09-20 Created: 2022-09-20 Last updated: 2023-09-21Bibliographically approved
Philipson, J., Awad, A., Lindström, L., Blomstedt, P., Jahanshahi, M. & Eriksson, J. (2023). Evaluation of the effects of DBS in the caudal Zona incerta on brain activity during a working memory task in patients with essential tremor. Neuroimage: Reports, 3(4), Article ID 100193.
Open this publication in new window or tab >>Evaluation of the effects of DBS in the caudal Zona incerta on brain activity during a working memory task in patients with essential tremor
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2023 (English)In: Neuroimage: Reports, ISSN 2666-9560, Vol. 3, no 4, article id 100193Article in journal (Refereed) Published
Abstract [en]

Essential tremor (ET) is characterized by bilateral upper limb postural and/or kinetic tremor, but also cognitive deficits. Tremor in ET, as well as aspects of cognitive deficits associated with ET, have been suggested to be linked to dysfunction in the cerebello-thalamo-cerebral circuit. In ET patients with disabling and medically intractable motor symptoms, Deep Brain Stimulation (DBS) is effective in reducing tremor. DBS in the caudal Zona incerta (cZi) has been shown to modulate the activity of the sensorimotor cerebello-cerebral circuit during motor tasks. Whether the activity in the cerebello-cerebral circuit is modulated by DBS during tasks involving working memory is unknown. The present study therefore aimed to investigate the possible effects of cZi DBS on working-memory processing in ET patients by means of task-based blood oxygen level-dependent (BOLD) fMRI.

Thirteen ET patients completed a working-memory task during DBS OFF and ON conditions. The task involved three conditions: maintenance, manipulation, and control. Behaviorally, there was no significant effect from DBS on accuracy, but a marginally significant Task x DBS interaction was detected for response times (RTs). However, post hoc comparisons for each condition failed to reach statistical significance. FMRI analyses revealed that DBS did not alter BOLD signal in regions of interest (lateral prefrontal cortex, parietal cortex, and the cerebellum), or in a complementary whole-brain analysis.

The present study indicates that DBS in the cZi in patients with ET has at most marginal effects on working memory, which is consistent with the results of pre- and post-DBS neuropsychological assessment showing minimal cognitive effects of surgery.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
Deep brain stimulation, Essential tremor, Working memory, fMRI
National Category
Neurosciences
Research subject
Neurology
Identifiers
urn:nbn:se:umu:diva-204363 (URN)10.1016/j.ynirp.2023.100193 (DOI)2-s2.0-85175237822 (Scopus ID)
Funder
Swedish Research Council
Note

Originally included in thesis in manuscript form.

Available from: 2023-02-02 Created: 2023-02-02 Last updated: 2023-11-09Bibliographically approved
Nordin, T., Blomstedt, P., Hemm, S. & Wårdell, K. (2023). How sample size impacts probabilistic stimulation maps in deep brain stimulation. Brain Sciences, 13(5), Article ID 756.
Open this publication in new window or tab >>How sample size impacts probabilistic stimulation maps in deep brain stimulation
2023 (English)In: Brain Sciences, E-ISSN 2076-3425, Vol. 13, no 5, article id 756Article in journal (Refereed) Published
Abstract [en]

Probabilistic stimulation maps of deep brain stimulation (DBS) effect based on voxel-wise statistics (p-maps) have increased in literature over the last decade. These p-maps require correction for Type-1 errors due to multiple testing based on the same data. Some analyses do not reach overall significance, and this study aims to evaluate the impact of sample size on p-map computation. A dataset of 61 essential tremor patients treated with DBS was used for the investigation. Each patient contributed with four stimulation settings, one for each contact. From the dataset, 5 to 61 patients were randomly sampled with replacement for computation of p-maps and extraction of high- and low-improvement volumes. For each sample size, the process was iterated 20 times with new samples generating in total 1140 maps. The overall p-value corrected for multiple comparisons, significance volumes, and dice coefficients (DC) of the volumes within each sample size were evaluated. With less than 30 patients (120 simulations) in the sample, the variation in overall significance was larger and the median significance volumes increased with sample size. Above 120 simulations, the trends stabilize but present some variations in cluster location, with a highest median DC of 0.73 for n = 57. The variation in location was mainly related to the region between the high- and low-improvement clusters. In conclusion, p-maps created with small sample sizes should be evaluated with caution, and above 120 simulations in single-center studies are probably required for stable results.

Place, publisher, year, edition, pages
MDPI, 2023
Keywords
deep brain stimulation (DBS), electric field simulation, finite element method (FEM), probabilistic stimulation maps (PSM)
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-209167 (URN)10.3390/brainsci13050756 (DOI)000995614300001 ()37239228 (PubMedID)2-s2.0-85160253561 (Scopus ID)
Funder
Swedish Foundation for Strategic Research, BD15-0032Swedish Research Council, 2016-03564
Available from: 2023-06-22 Created: 2023-06-22 Last updated: 2024-07-04Bibliographically approved
Stenmark Persson, R., Fytagoridis, A., Ryzhkov, M., Hariz, M. & Blomstedt, P. (2023). Long-term follow-up of unilateral deep brain stimulation targeting the caudal zona incerta in 13 patients with parkinsonian tremor. Stereotactic and Functional Neurosurgery, 101(6), 369-379
Open this publication in new window or tab >>Long-term follow-up of unilateral deep brain stimulation targeting the caudal zona incerta in 13 patients with parkinsonian tremor
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2023 (English)In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 101, no 6, p. 369-379Article in journal (Refereed) Published
Abstract [en]

Introduction: Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease (PD) and other movement disorders. The ventral intermediate nucleus of the thalamus (Vim) is considered as the target of choice for tremor disorders, including tremor-dominant PD not suitable for DBS in the subthalamic nucleus (STN). In the last decade, several studies have shown promising results on tremor from DBS in the posterior subthalamic area (PSA), including the caudal zona incerta (cZi) located postero-medial to the STN. The aim of this study was to evaluate the long-term effect of unilateral cZi/PSA-DBS in patients with tremor-dominant Parkinson’s disease.

Methods: Thirteen patients with PD with medically refractory tremor were included. The patients were evaluated using the motor part of the Unified Parkinson Disease Rating Scale (UPDRS) off/on medication before surgery and off/on medication and stimulation 1-2 years (short-term) after surgery and at a minimum of 3 years after surgery (long-term).

Results: At short-term follow-up DBS improved contralateral tremor by 88% in the off-medication state. This improvement persisted after a mean of 62 months. Contralateral bradykinesia was improved by 40% at short-term and 20% at long-term follow-up and the total UPDRS-III by 33% at short-term and by 22% at long-term follow-up with stimulation alone.

Conclusions: Unilateral cZi/PSA-DBS seems to remain an effective treatment for patients with severe Parkinsonian tremor several years after surgery. There was also a modest improvement on bradykinesia. 

Place, publisher, year, edition, pages
S. Karger, 2023
Keywords
Deep brain stimulation, Parkinson’s disease, Zona incerta, Tremor, Volume of tissue activated
National Category
Neurology Neurosciences
Research subject
Neurology; Neurosurgery
Identifiers
urn:nbn:se:umu:diva-216406 (URN)10.1159/000533793 (DOI)37879313 (PubMedID)2-s2.0-85178594623 (Scopus ID)
Funder
Umeå UniversityParkinsonfonden
Available from: 2023-11-10 Created: 2023-11-10 Last updated: 2023-12-15Bibliographically approved
Hariz, M., Cif, L. & Blomstedt, P. (2023). Thirty years of global deep brain stimulation: "plus ça change, plus c'est la même chose"?. Stereotactic and Functional Neurosurgery, 101(6), 395-406
Open this publication in new window or tab >>Thirty years of global deep brain stimulation: "plus ça change, plus c'est la même chose"?
2023 (English)In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 101, no 6, p. 395-406Article, review/survey (Refereed) Published
Abstract [en]

Background: The advent of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for Parkinson's disease 30 years ago has ushered a global breakthrough of DBS as a universal method for therapy and research in wide areas of neurology and psychiatry. The literature of the last three decades has described numerous concepts and practices of DBS, often branded as novelties or discoveries. However, reading the contemporary publications often elicits a sense of déjà vu in relation to several methods, attributes, and practices of DBS. Here, we review various applications and techniques of the modern-era DBS and compare them with practices of the past.

Summary: Compared with modern literature, publications of the old-era functional stereotactic neurosurgery, including old-era DBS, show that from the very beginning multidisciplinarity and teamwork were often prevalent and insisted upon, ethical concerns were recognized, brain circuitries and rational for brain targets were discussed, surgical indications were similar, closed-loop stimulation was attempted, evaluations of surgical results were debated, and controversies were common. Thus, it appears that virtually everything done today in the field of DBS bears resemblance to old-Time practices, or has been done before, albeit with partly other tools and techniques. Movement disorders remain the main indications for modern DBS as was the case for lesional surgery and old-era DBS. The novelties today consist of the STN as the dominant target for DBS, the tremendous advances in computerized brain imaging, the sophistication and versatility of implantable DBS hardware, and the large potential for research.

Key Messages: Many aspects of contemporary DBS bear strong resemblance to practices of the past. The dominant clinical indications remain movement disorders with virtually the same brain targets as in the past, with one exception: The STN. Other novel brain targets-that are so far subject to DBS trials-are the pedunculopontine nucleus for gait freezing, the anteromedial internal pallidum for Gilles de la Tourette and the fornix for Alzheimer's disease. The major innovations and novelties compared to the past concern mainly the unmatched level of research activity, its high degree of sponsorship, and the outstanding advances in technology that have enabled multimodal brain imaging and the miniaturization, versatility, and sophistication of implantable hardware. The greatest benefit for patients today, compared to the past, is the higher level of precision and safety of DBS, and of all functional stereotactic neurosurgery.

Place, publisher, year, edition, pages
S. Karger, 2023
Keywords
Deep brain stimulation, Depth electrodes, Ethics, Functional neurosurgery, History, Lesion, Multidisciplinarity, Parkinson's disease, Subthalamic nucleus
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-216655 (URN)10.1159/000533430 (DOI)37844558 (PubMedID)2-s2.0-85175805744 (Scopus ID)
Available from: 2023-11-28 Created: 2023-11-28 Last updated: 2024-01-08Bibliographically approved
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