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Awad, Amar
Publications (10 of 11) 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
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
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
Awad, A. (2022). Functional brain imaging of sensorimotor dysfunction and restoration: investigations of discomplete spinal cord injury and deep brain stimulation for essential tremor. (Doctoral dissertation). Umeå: Umeå University
Open this publication in new window or tab >>Functional brain imaging of sensorimotor dysfunction and restoration: investigations of discomplete spinal cord injury and deep brain stimulation for essential tremor
2022 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Funktionell hjärnavbildning av sensorimotorisk dysfunktion och behandling : undersökningar av diskompletta ryggmärgsskador och djup hjärnstimulering vid essentiell tremor
Abstract [en]

The nervous system exists to generate adaptive behaviour by processing sensory input from the body and the environment in order to produce appropriate motor output, and vice versa. Consequently, sensorimotor dysfunction is the basis of disability in most neurological pathologies. In the current thesis, I explore two conditions with different types and degrees of sensorimotor dysfunction by means of functional magnetic resonance imaging (fMRI). In part 1, I assess residual sensory connections to the brain in clinically complete spinal cord injury (SCI) with seemingly complete loss of sensorimotor function below the injury level. In part 2, fMRI is combined with deep brain stimulation (DBS) to investigate interventional mechanisms of restoring dysfunctional sensorimotor control in essential tremor (ET).

Part 1: SCI disrupts the communication between the brain and below-injury body parts, but rarely results in complete anatomical transection of the spinal cord. In studies I and II, we demonstrate somatosensory cortex activation due to somatosensory (tactile and nociceptive) stimulation on below-level insensate body parts in clinically complete SCI. The results from studies I and II indicate preserved somatosensory conduction across the spinal lesion in some cases of clinically complete SCI, as classified according to international standards. This subgroup is referred to as sensory discomplete SCI, which represents a distinct injury phenotype with an intermediate degree of injury severity between clinically complete and incomplete SCI.

Part 2: ET is effectively treated with DBS in the caudal zona incerta, but the neural mechanisms underlying the treatment effect are poorly understood. By exploring DBS mechanisms with fMRI, DBS was shown to cause modulation in the activity of the sensorimotor cerebello-cerebral regions during motor tasks (study III), but did not modulate the functional connectivity during resting-state (study IV).

fMRI is a valuable tool to investigate sensorimotor dysfunction and restoration in SCI and DBS-treated ET. There is evidence for sensory discomplete SCI in about half of the patients with clinically complete SCI. DBS modulates DBS modulation of the activity in the sensorimotor cerebello-cerebral circuit during motor tasks, but not during resting-state, is action-dependent.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2022. p. 136
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2194
Keywords
Sensorimotor control, fMRI, discomplete spinal cord injury, essential tremor, deep brain stimulation, cerebello-thalamo-cerebral circuit
National Category
Neurosciences Neurology
Research subject
Physiology; Neurosurgery; Neurology; Rehabilitation Medicine
Identifiers
urn:nbn:se:umu:diva-197840 (URN)978-91-7855-837-7 (ISBN)978-91-7855-838-4 (ISBN)
Public defence
2022-08-29, Hörsal Betula, Målpunkt L, Norrlands universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2022-08-16 Created: 2022-07-14 Last updated: 2022-08-09Bibliographically approved
Ågren, R., Awad, A., Blomstedt, P. & Fytagoridis, A. (2021). Voxel-Based Morphometry of Cerebellar Lobules in Essential Tremor. Frontiers in Aging Neuroscience, 13, Article ID 667854.
Open this publication in new window or tab >>Voxel-Based Morphometry of Cerebellar Lobules in Essential Tremor
2021 (English)In: Frontiers in Aging Neuroscience, E-ISSN 1663-4365, Vol. 13, article id 667854Article in journal (Refereed) Published
Abstract [en]

Background: The extent of neurodegeneration underlying essential tremor (ET) remains a matter of debate. Despite various extents of cerebellar atrophy on structural magnetic resonance imaging (MRI), previous studies have shown substantial heterogeneity and included a limited number of patients. Novel automated pipelines allow detailed segmentation of cerebellar lobules based on structural MRI. Objective: To compare the volumes of cerebellar lobules in ET patients with those in healthy controls (HCs) using an automated segmentation pipeline. Methods: Structural MRI scans of ET patients eligible for deep brain stimulation (n = 55) and of age-matched and gender-matched HCs (n = 55, from the IXI database) were segmented using the automated CEREbellum Segmentation pipeline. Lobule-specific volume differences between the ET and HC groups were evaluated using a general linear model corrected for multiple tests. Results: Total brain tissue volumes did not differ between the ET and HC groups. ET patients demonstrated reduced volumes of lobules I-II, left Crus II, left VIIB, and an increased volume of right X when compared with the HC group. Conclusion: A large cohort of ET patients demonstrated subtle signs of decreased cerebellar lobule volumes. These findings oppose the hypothesis of localized atrophy in cerebellar motor areas in ET, but not the possibility of cerebellar pathophysiology in ET. Prospective investigations using alternative neuroimaging modalities may further elucidate the pathophysiology of ET and provide insights into diagnostic and therapeutic approaches.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2021
Keywords
cerebellum, essential tremor, lobule volume, structural MRI, voxel-based morphometry
National Category
Neurosciences Radiology, Nuclear Medicine and Medical Imaging Neurology
Research subject
Neurosurgery
Identifiers
urn:nbn:se:umu:diva-185747 (URN)10.3389/fnagi.2021.667854 (DOI)000664968300001 ()34177554 (PubMedID)2-s2.0-85108719695 (Scopus ID)
Available from: 2021-07-05 Created: 2021-07-05 Last updated: 2024-07-04Bibliographically approved
Awad, A., Blomstedt, P., Westling, G. & Eriksson, J. (2020). Deep brain stimulation in the caudal zona incerta modulates the sensorimotor cerebello-cerebral circuit in essential tremor. NeuroImage, 209, Article ID 116511.
Open this publication in new window or tab >>Deep brain stimulation in the caudal zona incerta modulates the sensorimotor cerebello-cerebral circuit in essential tremor
2020 (English)In: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 209, article id 116511Article in journal (Refereed) Published
Abstract [en]

Essential tremor is effectively treated with deep brain stimulation (DBS), but the neural mechanisms underlying the treatment effect are poorly understood. Essential tremor is driven by a dysfunctional cerebello-thalamo-cerebral circuit resulting in pathological tremor oscillations. DBS is hypothesised to interfere with these oscillations at the stimulated target level, but it is unknown whether the stimulation modulates the activity of the cerebello-thalamo-cerebral circuit during different task states (with and without tremor) in awake essential tremor patients. To address this issue, we used functional MRI in 16 essential tremor patients chronically implanted with DBS in the caudal zona incerta. During scanning, the patients performed unilateral tremor-inducing postural holding and pointing tasks as well as rest, with contralateral stimulation turned On and Off.

We show that DBS exerts both task-dependent as well as task-independent modulation of the sensorimotor cerebello-cerebral regions (p ​≤ ​0.05, FWE cluster-corrected for multiple comparisons). Task-dependent modulation (DBS ​× ​task interaction) resulted in two patterns of stimulation effects. Firstly, activity decreases (blood oxygen level-dependent signal) during tremor-inducing postural holding in the primary sensorimotor cortex and cerebellar lobule VIII, and activity increases in the supplementary motor area and cerebellar lobule V during rest (p ​≤ ​0.05, post hoc two-tailed t-test). These effects represent differences at the effector level and may reflect DBS-induced tremor reduction since the primary sensorimotor cortex, cerebellum and supplementary motor area exhibit less motor task-activity as compared to the resting condition during On stimulation. Secondly, task-independent modulation (main effect of DBS) was observed as activity increase in the lateral premotor cortex during all motor tasks, and also during rest (p ​≤ ​0.05, post hoc two-tailed t-test). This task-independent effect may mediate the therapeutic effects of DBS through the facilitation of the premotor control over the sensorimotor circuit, making it less susceptible to tremor entrainment.

Our findings support the notion that DBS in essential tremor is modulating the sensorimotor cerebello-cerebral circuit, distant to the stimulated target, and illustrate the complexity of stimulation mechanisms by demonstrating task-dependent as well as task-independent actions in cerebello-cerebral regions.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Essential tremor, Deep brain stimulation, Caudal zona incerta, Functional MRI, Cerebello-cerebral circuit
National Category
Neurology Physiology Neurosciences
Research subject
Neurosurgery; Neurology; Physiology
Identifiers
urn:nbn:se:umu:diva-167200 (URN)10.1016/j.neuroimage.2019.116511 (DOI)000517885100011 ()31901420 (PubMedID)2-s2.0-85077302888 (Scopus ID)
Funder
Västerbotten County Council
Available from: 2020-01-11 Created: 2020-01-11 Last updated: 2023-03-24Bibliographically approved
Awad, A., Levi, R., Waller, M., Westling, G., Lindgren, L. & Eriksson, J. (2020). Preserved somatosensory conduction in complete spinal cord injury: Discomplete SCI. Clinical Neurophysiology, 131(5), 1059-1067
Open this publication in new window or tab >>Preserved somatosensory conduction in complete spinal cord injury: Discomplete SCI
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2020 (English)In: Clinical Neurophysiology, ISSN 1388-2457, E-ISSN 1872-8952, Vol. 131, no 5, p. 1059-1067Article in journal (Refereed) Published
Abstract [en]

Objective: Spinal cord injury (SCI) disrupts the communication between brain and body parts innervated from below-injury spinal segments, but rarely results in complete anatomical transection of the spinal cord. The aim of this study was to investigate residual somatosensory conduction in clinically complete SCI, to corroborate the concept of sensory discomplete SCI.

Methods: We used fMRI with a somatosensory protocol in which blinded and randomized tactile and nociceptive stimulation was applied on both legs (below-injury level) and one arm (above-injury level) in eleven participants with chronic complete SCI. The experimental design accounts for possible confounding mechanical (e.g. vibration) and cortico-cortical top-down mechanisms (e.g. attention/expectation).

Results: Somatosensory stimulation on below-level insensate body regions activated the somatotopically corresponding part of the contralateral primary somatosensory cortex in six out of eleven participants.

Conclusions: Our results represent afferent-driven cortical activation through preserved somatosensory connections to the brain in a subgroup of participants with clinically complete SCI, i.e. sensory discomplete SCI.

Significance: Identifying patients with residual somatosensory connections might open the door for new rehabilitative and restorative strategies as well as inform research on SCI-related conditions such as neuropathic pain and spasticity.

Place, publisher, year, edition, pages
Elsevier, 2020
Keywords
Spinal cord injury, Functional MRI, Somatosensory, Discomplete, Non-conscious
National Category
Neurology Neurosciences Physiology
Research subject
Neurology; Neurosurgery; Rehabilitation Medicine; Physiology
Identifiers
urn:nbn:se:umu:diva-169138 (URN)10.1016/j.clinph.2020.01.017 (DOI)000525862400011 ()32197128 (PubMedID)2-s2.0-85082123930 (Scopus ID)
Available from: 2020-03-22 Created: 2020-03-22 Last updated: 2022-07-15Bibliographically approved
Awad, A., Blomstedt, P., Westling, G. & Eriksson, J. (2017). Functional imaging of Essential Tremor treated with Deep Brain Stimulation In the caudal Zona incerta. In: : . Paper presented at 17th Quadrennial Meeting of the World Society for Stereotactic and Functional Neurosurgery (WSSFN), Berlin, June 26-29, 2017. Berlin
Open this publication in new window or tab >>Functional imaging of Essential Tremor treated with Deep Brain Stimulation In the caudal Zona incerta
2017 (English)Conference paper, Oral presentation with published abstract (Refereed)
Place, publisher, year, edition, pages
Berlin: , 2017
National Category
Neurosciences
Research subject
Neurosurgery; Physiology; Neurology
Identifiers
urn:nbn:se:umu:diva-163719 (URN)
Conference
17th Quadrennial Meeting of the World Society for Stereotactic and Functional Neurosurgery (WSSFN), Berlin, June 26-29, 2017
Available from: 2019-10-02 Created: 2019-10-02 Last updated: 2021-04-07Bibliographically approved
Awad, A., Levi, R., Lindgren, L., Hultling, C., Westling, G., Nyberg, L. & Eriksson, J. (2015). Preserved somatosensory conduction in a patient with complete cervical spinal cord injury. Journal of Rehabilitation Medicine, 47(5), 426-431
Open this publication in new window or tab >>Preserved somatosensory conduction in a patient with complete cervical spinal cord injury
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2015 (English)In: Journal of Rehabilitation Medicine, ISSN 1650-1977, E-ISSN 1651-2081, Vol. 47, no 5, p. 426-431Article in journal (Refereed) Published
Abstract [en]

Objective: Neurophysiological investigation has shown that patients with clinically complete spinal cord injury can have residual motor sparing ("motor discomplete"). In the current study somatosensory conduction was assessed in a patient with clinically complete spinal cord injury and a novel ethodology for assessing such preservation is described, in this case indicating "sensory discomplete" spinal cord injury. Methods: Blood oxygenation level-dependent functional magnetic resonance imaging (BOLD fMRI) was used to examine the somatosensory system in a healthy subject and in a subject with a clinically complete cervical spinal cord injury, by applying tactile stimulation above and below the level of spinal cord injury, with and without visual feedback. Results: In the participant with spinal cord injury, somatosensory stimulation below the neurological level of the lesion gave rise to BOLD signal changes in the corresponding areas of the somatosensory cortex. Visual feedback of the stimulation strongly modulated the somatosensory BOLD signal, implying that cortico-cortical rather than spino-cortical connections can drive activity in the somatosensory cortex. Critically, BOLD signal change was also evident when the visual feedback of the stimulation was removed, thus demonstrating sensory discomplete spinal cord injury. Conclusion: Given the existence of sensory discomplete spinal cord injury, preserved but hitherto undetected somatosensory conduction might contribute to the unexplained variability related to, for example, the propensity to develop decubitus ulcers and neuropathic pain among patients with clinically complete spinal cord injury.

Place, publisher, year, edition, pages
Foundation of Rehabilitation Information, 2015
Keywords
fMRI, spinal cord injury, complete, non-conscious, somatosensory cortex
National Category
Sport and Fitness Sciences Physiotherapy
Identifiers
urn:nbn:se:umu:diva-105263 (URN)10.2340/16501977-1955 (DOI)000355371600006 ()25808357 (PubMedID)2-s2.0-84928235399 (Scopus ID)
Available from: 2015-06-22 Created: 2015-06-22 Last updated: 2023-03-24Bibliographically approved
Awad, A. (2015). Ryggmärgsskador av ”discomplete” -typ och smärta. BestPractice Nordic, 6(12), 6-9
Open this publication in new window or tab >>Ryggmärgsskador av ”discomplete” -typ och smärta
2015 (Swedish)In: BestPractice Nordic, Vol. 6, no 12, p. 6-9Article in journal (Other academic) Published
National Category
Neurosciences Physiology
Research subject
Rehabilitation Medicine; Physiology; Neurology
Identifiers
urn:nbn:se:umu:diva-163721 (URN)
Available from: 2019-10-02 Created: 2019-10-02 Last updated: 2019-10-08Bibliographically approved
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