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Functional brain imaging of sensorimotor dysfunction and restoration: investigations of discomplete spinal cord injury and deep brain stimulation for essential tremor
Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
2022 (English)Doctoral thesis, comprehensive summary (Other academic)Alternative title
Funktionell hjärnavbildning av sensorimotorisk dysfunktion och behandling : undersökningar av diskompletta ryggmärgsskador och djup hjärnstimulering vid essentiell tremor (Swedish)
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 [en]
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: urn:nbn:se:umu:diva-197840ISBN: 978-91-7855-837-7 (print)ISBN: 978-91-7855-838-4 (electronic)OAI: oai:DiVA.org:umu-197840DiVA, id: diva2:1683298
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
List of papers
1. Preserved somatosensory conduction in a patient with complete cervical spinal cord injury
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
2. Preserved somatosensory conduction in complete spinal cord injury: Discomplete SCI
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
3. Deep brain stimulation in the caudal zona incerta modulates the sensorimotor cerebello-cerebral circuit in essential tremor
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
4. Deep brain stimulation does not modulate fMRI resting- state functional connectivity in essential tremor
Open this publication in new window or tab >>Deep brain stimulation does not modulate fMRI resting- state functional connectivity in essential tremor
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(English)Manuscript (preprint) (Other academic)
National Category
Neurosciences Neurology
Research subject
Physiology; Neurosurgery; Neurology
Identifiers
urn:nbn:se:umu:diva-197808 (URN)
Available from: 2022-07-05 Created: 2022-07-05 Last updated: 2022-08-09

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