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Hariz, Marwan
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Akram, H., Dayal, V., Mahlknecht, P., Georgiev, D., Hyam, J., Foltynie, T., . . . Zrinzo, L. (2018). Connectivity derived thalamic segmentation in deep brain stimulation for tremor. NeuroImage: Clinical, 18, 130-142
Open this publication in new window or tab >>Connectivity derived thalamic segmentation in deep brain stimulation for tremor
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2018 (English)In: NeuroImage: Clinical, ISSN 0353-8842, E-ISSN 2213-1582, Vol. 18, p. 130-142Article in journal (Refereed) Published
Abstract [en]

The ventral intermediate nucleus (VIM) of the thalamus is an established surgical target for stereotactic ablation and deep brain stimulation (DBS) in the treatment of tremor in Parkinson's disease (PD) and essential tremor (ET). It is centrally placed on a cerebello-thalamo-cortical network connecting the primary motor cortex, to the dentate nucleus of the contralateral cerebellum through the dentato-rubro-thalamic tract (DRT). The VIM is not readily visible on conventional MR imaging, so identifying the surgical target traditionally involved indirect targeting that relies on atlas-defined coordinates. Unfortunately, this approach does not fully account for individual variability and requires surgery to be performed with the patient awake to allow for intraoperative targeting confirmation. The aim of this study is to identify the VIM and the DRT using probabilistic tractography in patients that will undergo thalamic DBS for tremor. Four male patients with tremor dominant PD and five patients (three female) with ET underwent high angular resolution diffusion imaging (HARDI) (128 diffusion directions, 1.5 mm isotropic voxels and b value = 1500) preoperatively. Patients received VIM-DBS using an MR image guided and MR image verified approach with indirect targeting. Postoperatively, using parallel Graphical Processing Unit (GPU) processing, thalamic areas with the highest diffusion connectivity to the primary motor area (M1), supplementary motor area (SMA), primary sensory area (S1) and contralateral dentate nucleus were identified. Additionally, volume of tissue activation (VTA) corresponding to active DBS contacts were modelled. Response to treatment was defined as 40% reduction in the total Fahn-Tolosa-Martin Tremor Rating Score (FTMTRS) with DBS-ON, one year from surgery. Three out of nine patients had a suboptimal, long-term response to treatment. The segmented thalamic areas corresponded well to anatomically known counterparts in the ventrolateral (VL) and ventroposterior (VP) thalamus. The dentate-thalamic area, lay within the M1-thalamic area in a ventral and lateral location. Streamlines corresponding to the DRT connected M1 to the contralateral dentate nucleus via the dentate-thalamic area, clearly crossing the midline in the mesencephalon. Good response was seen when the active contact VTA was in the thalamic area with highest connectivity to the contralateral dentate nucleus. Non-responders had active contact VTAs outside the dentate-thalamic area. We conclude that probabilistic tractography techniques can be used to segment the VL and VP thalamus based on cortical and cerebellar connectivity. The thalamic area, best representing the VIM, is connected to the contralateral dentate cerebellar nucleus. Connectivity based segmentation of the VIM can be achieved in individual patients in a clinically feasible timescale, using HARDI and high performance computing with parallel GPU processing. This same technique can map out the DRT tract with clear mesencephalic crossing.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Diffusion weighted imaging DWI, Connectivity, Parkinson's disease PD, Ventrointermedialis VIM, Dentato-rubro-thalamic tract DRT, Ventrolateral nucleus VL, Dentate nucleus Tremor, Deep brain stimulation DBS
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-151204 (URN)10.1016/j.nicl.2018.01.008 (DOI)000433169000013 ()29387530 (PubMedID)2-s2.0-85041484333 (Scopus ID)
Available from: 2018-09-03 Created: 2018-09-03 Last updated: 2018-09-03Bibliographically approved
Blomstedt, P., Stenmark Persson, R., Hariz, G.-M., Linder, J., Fredricks, A., Häggström, B., . . . Hariz, M. (2018). Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation. Journal of Neurology, Neurosurgery and Psychiatry, 89(7), 710-716
Open this publication in new window or tab >>Deep brain stimulation in the caudal zona incerta versus best medical treatment in patients with Parkinson's disease: a randomised blinded evaluation
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2018 (English)In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 89, no 7, p. 710-716Article in journal (Refereed) Published
Abstract [en]

Background: Several open-label studies have shown good effect of deep brain stimulation (DBS) in the caudal zona incerta (cZi) on tremor, including parkinsonian tremor, and in some cases also a benefit on akinesia and axial symptoms. The aim of this study was to evaluate objectively the effect of cZi DBS in patients with Parkinson's disease (PD).

Method: 25 patients with PD were randomised to either cZi DBS or best medical treatment. The primary outcomes were differences between the groups in the motor scores of the Unified Parkinson's Disease Rating Scale (UPDRS-III) rated single-blindly at 6 months and differences in the Parkinson's Disease Questionnaire 39 items (PDQ-39). 19 patients, 10 in the medical arm and 9 in the DBS arm, fulfilled the study.

Results: The DBS group had 41% better UPDRS-III scores off-medication on-stimulation compared with baseline, whereas the scores of the non-surgical patients off-medication were unchanged. In the on-medication condition, there were no differences between the groups, neither at baseline nor at 6 months. Subitems of the UPDRS-III showed a robust effect of cZi DBS on tremor. The PDQ-39 domains 'stigma' and 'ADL' improved only in the DBS group. The PDQ-39 summary index improved in both groups.

Conclusion: This is the first randomised blinded evaluation of cZi DBS showing its efficacy on PD symptoms. The most striking effect was on tremor; however, the doses of dopaminergic medications could not be decreased. cZi DBS in PD may be an addition to existing established targets, enabling tailoring the surgery to the needs of the individual patient.

Place, publisher, year, edition, pages
BMJ Publishing Group Ltd, 2018
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-150375 (URN)10.1136/jnnp-2017-317219 (DOI)000438044100010 ()29386253 (PubMedID)
Available from: 2018-08-08 Created: 2018-08-08 Last updated: 2018-08-08Bibliographically approved
Martinez-Ramirez, D., Jimenez-Shahed, J., Leckman, J. F., Porta, M., Servello, D., Meng, F.-G., . . . Okun, M. S. (2018). Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry. JAMA Neurology, 75(3), 353-359
Open this publication in new window or tab >>Efficacy and Safety of Deep Brain Stimulation in Tourette Syndrome: The International Tourette Syndrome Deep Brain Stimulation Public Database and Registry
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2018 (English)In: JAMA Neurology, ISSN 2168-6149, E-ISSN 2168-6157, Vol. 75, no 3, p. 353-359Article in journal (Refereed) Published
Abstract [en]

IMPORTANCE Collective evidence has strongly suggested that deep brain stimulation (DBS) is a promising therapy for Tourette syndrome.

OBJECTIVE To assess the efficacy and safety of DBS in a multinational cohort of patients with Tourette syndrome.

DESIGN, SETTING, AND PARTICIPANTS The prospective International Deep Brain Stimulation Database and Registry included 185 patients with medically refractory Tourette syndrome who underwent DBS implantation from January 1, 2012, to December 31, 2016, at 31 institutions in 10 countries worldwide.

EXPOSURES Patients with medically refractory symptoms received DBS implantation in the centromedian thalamic region (93 of 163 [57.1%]), the anterior globus pallidus internus (41 of 163 [25.2%]), the posterior globus pallidus internus (25 of 163 [15.3%]), and the anterior limb of the internal capsule (4 of 163 [2.5%]).

MAIN OUTCOMES AND MEASURES Scores on the Yale Global Tic Severity Scale and adverse events.

RESULTS The International Deep Brain Stimulation Database and Registry enrolled 185 patients (of 171 with available data, 37 females and 134 males; mean [SD] age at surgery, 29.1 [10.8] years [range, 13-58 years]). Symptoms of obsessive-compulsive disorder were present in 97 of 151 patients (64.2%) and 32 of 148 (21.6%) had a history of self-injurious behavior. The mean (SD) total Yale Global Tic Severity Scale score improved from 75.01 (18.36) at baseline to 41.19 (20.00) at 1 year after DBS implantation (P<.001). The mean (SD) motor tic subscore improved from 21.00 (3.72) at baseline to 12.91 (5.78) after 1 year (P <.001), and the mean (SD) phonic tic subscore improved from 16.82 (6.56) at baseline to 9.63 (6.99) at 1 year (P <.001). The overall adverse event rate was 35.4%(56 of 158 patients), with intracranial hemorrhage occurring in 2 patients (1.3%), infection in 4 patients with 5 events (3.2%), and lead explantation in 1 patient (0.6%). The most common stimulation-induced adverse effects were dysarthria (10 [6.3%]) and paresthesia (13 [8.2%]).

CONCLUSIONS AND RELEVANCE Deep brain stimulationwas associated with symptomatic improvement in patients with Tourette syndrome but also with important adverse events. A publicly available website on outcomes of DBS in patients with Tourette syndrome has been provided.

Place, publisher, year, edition, pages
American Medical Association, 2018
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-146451 (URN)10.1001/jamaneurol.2017.4317 (DOI)000427265700013 ()29340590 (PubMedID)
Note

En rättelse har publicerats: / A correction has been published:

Error in abstract. (2018). JAMA Neurology, 75(3), 384-384. doi:10.1001/jamaneurol.2018.0060

Available from: 2018-05-03 Created: 2018-05-03 Last updated: 2018-06-09Bibliographically approved
Blomstedt, P. & Hariz, M. (2018). The paper that wrote itself – A ghost story [Letter to the editor]. Movement Disorders, 33(9), 1509-1510
Open this publication in new window or tab >>The paper that wrote itself – A ghost story
2018 (English)In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 33, no 9, p. 1509-1510Article in journal, Letter (Refereed) Published
Place, publisher, year, edition, pages
John Wiley & Sons, 2018
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-153138 (URN)10.1002/mds.27467 (DOI)000447153500025 ()30199595 (PubMedID)2-s2.0-85054727411 (Scopus ID)
Available from: 2018-11-08 Created: 2018-11-08 Last updated: 2018-11-08Bibliographically approved
Pepper, J., Meliak, L., Akram, H., Hyam, J., Milabo, C., Candelario, J., . . . Zrinzo, L. (2017). Changing of the guard: reducing infection when replacing neural pacemakers. Journal of Neurosurgery, 126(4), 1165-1172
Open this publication in new window or tab >>Changing of the guard: reducing infection when replacing neural pacemakers
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2017 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 126, no 4, p. 1165-1172Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE Infection of deep brain stimulation (DBS) hardware has a significant impact on patient morbidity. Previous experience suggests that infection rates appear to be higher after implantable pulse generator (IPG) replacement surgery than after the de novo DBS procedure. In this study the authors examine the effect of a change in practice during DBS IPG replacements at their institution. METHODS Starting in January 2012, patient screening for methicillin-resistant Staphylococcus aureus (MRSA) and, and where necessary, eradication was performed prior to elective DBS IPG change. Moreover, topical vancomycin was placed in the IPG pocket during surgery. The authors then prospectively examined the infection rate in patients undergoing DBS IPG replacement at their center over a 3-year period with at least 9 months of follow-up. RESULTS The total incidence of infection in this prospective consecutive series of 101 IPG replacement procedures was 0%, with a mean follow-up duration of 24 +/- 11 months. This was significantly lower than the authors' previously published historical control group, prior to implementing the change in practice, where the infection rate for IPG replacement was 8.5% (8/94 procedures; p = 0.003). CONCLUSIONS This study suggests that a change in clinical practice can significantly lower infection rates in patients undergoing DBS IPG replacement. These simple measures can minimize unnecessary surgery, loss of benefit from chronic stimulation, and costly hardware replacement, further improving the cost efficacy of DBS therapies.

Place, publisher, year, edition, pages
AMER ASSOC NEUROLOGICAL SURGEONS, 2017
Keywords
deep brain stimulation, implantable pulse generator, infection, Parkinson's disease, reoperation, antibiotic, vancomycin, functional neurosurgery
National Category
Surgery Neurology
Identifiers
urn:nbn:se:umu:diva-134243 (URN)10.3171/2016.4.JNS152934 (DOI)000397837900018 ()27315022 (PubMedID)
Available from: 2017-05-29 Created: 2017-05-29 Last updated: 2018-06-09Bibliographically approved
Pepper, J., Meliak, L., Akram, H., Hyam, J., Milabo, C., Candelario, J., . . . Zrinzo, L. (2017). Changing of the guard: reducing infection when replacing neural pacemakers. Journal of Neurosurgery, 126(4), 1165-1172
Open this publication in new window or tab >>Changing of the guard: reducing infection when replacing neural pacemakers
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2017 (English)In: Journal of Neurosurgery, ISSN 0022-3085, E-ISSN 1933-0693, Vol. 126, no 4, p. 1165-1172Article in journal (Refereed) Published
Abstract [en]

OBJECTIVE Infection of deep brain stimulation (DBS) hardware has a significant impact on patient morbidity. Previous experience suggests that infection rates appear to be higher after implantable pulse generator (IPG) replacement surgery than after the de novo DBS procedure. In this study the authors examine the effect of a change in practice during DBS IPG replacements at their institution. METHODS Starting in January 2012, patient screening for methicillin-resistant Staphylococcus aureus (MRSA) and, and where necessary, eradication was performed prior to elective DBS IPG change. Moreover, topical vancomycin was placed in the IPG pocket during surgery. The authors then prospectively examined the infection rate in patients undergoing DBS IPG replacement at their center over a 3-year period with at least 9 months of follow-up. RESULTS The total incidence of infection in this prospective consecutive series of 101 IPG replacement procedures was 0%, with a mean follow-up duration of 24 ± 11 months. This was significantly lower than the authors' previously published historical control group, prior to implementing the change in practice, where the infection rate for IPG replacement was 8.5% (8/94 procedures; p = 0.003). CONCLUSIONS This study suggests that a change in clinical practice can significantly lower infection rates in patients undergoing DBS IPG replacement. These simple measures can minimize unnecessary surgery, loss of benefit from chronic stimulation, and costly hardware replacement, further improving the cost efficacy of DBS therapies.

Keywords
DBS = deep brain stimulation, IPG = implantable pulse generator, MRSA = methicillin-resistant Staphylococcus aureus, Parkinson's disease, antibiotic, deep brain stimulation, functional neurosurgery, implantable pulse generator, infection, reoperation, vancomycin
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-134629 (URN)10.3171/2016.4.JNS152934 (DOI)000397837900018 ()27315022 (PubMedID)
Available from: 2017-05-10 Created: 2017-05-10 Last updated: 2018-06-09Bibliographically approved
Vanhoecke, J. & Hariz, M. (2017). Deep brain stimulation for disorders of consciousness: Systematic review of cases and ethics. Brain Stimulation, 10(6), 1013-1023
Open this publication in new window or tab >>Deep brain stimulation for disorders of consciousness: Systematic review of cases and ethics
2017 (English)In: Brain Stimulation, ISSN 1935-861X, E-ISSN 1876-4754, Vol. 10, no 6, p. 1013-1023Article, review/survey (Refereed) Published
Abstract [en]

Background: A treatment for patients suffering from prolonged severely altered consciousness is not available. The success of Deep Brain Stimulation (DBS) in diseases such as Parkinson's, dystonia and essential tremor provided a renewed impetus for its application in Disorders of Consciousness (DoC). Objective: To evaluate the rationale for DBS in patients with DoC, through systematic review of literature containing clinical data and ethical considerations. Methods: Articles from PubMed, Embase, Medline and Web of Science were systematically reviewed. Results: The outcomes of 78 individual patients reported in 19 articles from 1968 onwards were pooled and elements of ethical discussions were compared. There is no clear clinical evidence that DBS is a treatment for DoC that can restore both consciousness and the ability to communicate. In patients who benefitted, the outcome of DBS is often confounded by the time frame of spontaneous recovery from DoC. Difficult ethical considerations remain, such as the risk of increasing self-awareness of own limitations, without improving overall wellbeing, and the issues of proxy consent. Conclusion: DBS is far from being evident as a possible future therapeutic avenue for patients with DoC. Double-blind studies are lacking, and many clinical and ethical issues have to be addressed. In the rare cases when DBS for patients with DoC is considered, this needs to be evaluated meticulously on a case by case basis, with comprehensive overall outcome measures including psychological and quality-of-life assessments, and with the guidance of an ethical and interdisciplinary panel, especially in relation to proxy consent. 

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Deep brain stimulation, Disorders of consciousness, Minimally conscious state, Vegetative state, ma, Neuroethics, Neuromodulation
National Category
Neurology Neurosciences
Identifiers
urn:nbn:se:umu:diva-141978 (URN)10.1016/j.brs.2017.08.006 (DOI)000414074400001 ()28966051 (PubMedID)
Available from: 2017-12-06 Created: 2017-12-06 Last updated: 2018-06-09Bibliographically approved
Naesström, M., Blomstedt, P., Hariz, M. & Bodlund, O. (2017). Deep brain stimulation for obsessive-compulsive disorder: knowledge and concerns among psychiatrists, psychotherapists and patients. Surgical neurology international, 8, Article ID 298.
Open this publication in new window or tab >>Deep brain stimulation for obsessive-compulsive disorder: knowledge and concerns among psychiatrists, psychotherapists and patients
2017 (English)In: Surgical neurology international, ISSN 2229-5097, Vol. 8, article id 298Article in journal (Refereed) Published
Abstract [en]

Background: Deep brain stimulation (DBS) is under investigation for severe obsessive-compulsive disorder (OCD) resistant to other therapies. The number of implants worldwide is slowly increasing. Therefore, it is of importance to explore knowledge and concerns of this novel treatment among patients and their psychiatric healthcare contacts. This information is relevant for scientific professionals working with clinical studies for DBS for this indication. Especially, for future study designs and the creation of information targeting healthcare professionals and patients. The aim of this study was to explore the knowledge and concerns toward DBS among patients with OCD, psychiatrists, and cognitive behavioral therapists.

Methods: The study was conducted through web-based surveys for the aimed target groups -psychiatrist, patients, and cognitive behavioral therapists. The surveys contained questions regarding previous knowledge of DBS, source of knowledge, attitudes, and concerns towards the therapy.

Results: The main source of information was from scientific sources among psychiatrists and psychotherapists. The patient's main source of information was the media. Common concerns among the groups included complications from surgery, anesthesia, stimulation side effects, and the novelty of the treatment. Specific concerns for the groups included; personality changes mentioned by patients and psychotherapists, and ethical concerns among psychiatrists.

Conclusion: There are challenges for DBS in OCD as identified by the participants of this study; source and quality of information, efficacy, potential adverse effects, and eligibility. In all of which the current evidence base still is limited. A broad research agenda is needed for studies going forward.

Place, publisher, year, edition, pages
Medknow Publications, 2017
Keywords
attitude, deep brain stimulation, obsessive-compulsive disorder, patient, psychiatrist, psychotherapist
National Category
Psychiatry
Identifiers
urn:nbn:se:umu:diva-146475 (URN)29285414 (PubMedID)
Available from: 2018-04-10 Created: 2018-04-10 Last updated: 2018-06-11Bibliographically approved
Georgiev, D., Hamberg, K., Hariz, M., Forsgren, L. & Hariz, G.-M. (2017). Gender differences in Parkinson's disease: a clinical perspective. Acta Neurologica Scandinavica, 136(6), 570-584
Open this publication in new window or tab >>Gender differences in Parkinson's disease: a clinical perspective
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2017 (English)In: Acta Neurologica Scandinavica, ISSN 0001-6314, E-ISSN 1600-0404, Vol. 136, no 6, p. 570-584Article in journal (Refereed) Published
Abstract [en]

Available data indicate that there are gender differences in many features of Parkinson's disease (PD). Precise identification of the gender differences is important to tailor treatment, predict outcomes, and meet other individual and social needs in women and men with PD. The aim of this study was to review the available clinical data on gender differences in PD. Original articles and meta-analyses published between 1990 and 2016 systematically exploring gender differences in PD were reviewed. There is slight male preponderance in incidence and prevalence of PD. PD starts earlier in men. Women tend to be more prone to develop tremor-dominant PD but are less rigid than men. Motor improvement after deep brain stimulation is equal in both sexes, but women tend to show better improvement in activities of daily living. Furthermore, women with PD show better results on tests for general cognitive abilities, outperform men in verbal cognitive tasks, show more pain symptoms, and score higher on depression scales. It seems, however, that the differences in cognition, mood, and pain perception are not disease specific as similar gender differences can be found in healthy subjects and in other neurological conditions. Despite PD being the most frequently studied movement disorder, studies investigating gender differences in PD are still scarce with most of the studies being cross-sectional. Good-quality, prospective, longitudinal studies analyzing gender differences in PD and comparing them to matched healthy controls are needed in order to properly address the issues of gender differences in PD.

Place, publisher, year, edition, pages
John Wiley & Sons, 2017
Keywords
activities of daily living, gender differences, motor symptoms, non-motor symptoms, Parkinson's disease, quality of life
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-140684 (URN)10.1111/ane.12796 (DOI)000414488000002 ()28670681 (PubMedID)
Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2018-06-09Bibliographically approved
Robertson, M. M., Eapen, V., Singer, H. S., Martino, D., Scharf, J. M., Paschou, P., . . . Leckman, J. F. (2017). Gilles de la Tourette syndrome. Nature reviews disease primers, 3, Article ID 16097.
Open this publication in new window or tab >>Gilles de la Tourette syndrome
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2017 (English)In: Nature reviews disease primers, ISSN 2056-676X, Vol. 3, article id 16097Article in journal (Refereed) Published
Abstract [en]

Gilles de la Tourette syndrome (GTS) is a childhood-onset neurodevelopmental disorder that is characterized by several motor and phonic tics. Tics usually develop before 10 years of age, exhibit a waxing and waning course and typically improve with increasing age. A prevalence of approximately 1% is estimated in children and adolescents. The condition can result in considerable social stigma and poor quality of life, especially when tics are severe (for example, with coprolalia (swearing tics) and self-injurious behaviours) or when GTS is accompanied by attention-deficit/hyperactivity disorder, obsessive-compulsive disorder or another neuropsychiatric disorder. The aetiology is complex and multifactorial. GTS is considered to be polygenic, involving multiple common risk variants combined with rare, inherited or de novo mutations. These as well as non-genetic factors (such as perinatal events and immunological factors) are likely to contribute to the heterogeneity of the clinical phenotype, the structural and functional brain anomalies and the neural circuitry involvement. Management usually includes psychoeducation and reassurance, behavioural methods, pharmacotherapy and, rarely, functional neurosurgery. Future research that integrates clinical and neurobiological data, including neuroimaging and genetics, is expected to reveal the pathogenesis of GTS at the neural circuit level, which may lead to targeted interventions.

Place, publisher, year, edition, pages
United Kingdom: Nature Publishing Group, 2017
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-133666 (URN)10.1038/nrdp.2016.97 (DOI)000397893000001 ()28150698 (PubMedID)
Available from: 2017-04-25 Created: 2017-04-25 Last updated: 2018-06-09Bibliographically approved
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