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Deep brain stimulation in the caudal zona incerta modulates the sensorimotor cerebello-cerebral circuit in essential tremor
Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).ORCID-id: 0000-0002-3068-0065
Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Klinisk neurovetenskap.
Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).
Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB).ORCID-id: 0000-0002-1407-9288
2020 (Engelska)Ingår i: NeuroImage, ISSN 1053-8119, E-ISSN 1095-9572, Vol. 209, artikel-id 116511Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Elsevier, 2020. Vol. 209, artikel-id 116511
Nyckelord [en]
Essential tremor, Deep brain stimulation, Caudal zona incerta, Functional MRI, Cerebello-cerebral circuit
Nationell ämneskategori
Neurologi Fysiologi Neurovetenskaper
Forskningsämne
neurokirurgi; neurologi; fysiologi
Identifikatorer
URN: urn:nbn:se:umu:diva-167200DOI: 10.1016/j.neuroimage.2019.116511ISI: 000517885100011PubMedID: 31901420Scopus ID: 2-s2.0-85077302888OAI: oai:DiVA.org:umu-167200DiVA, id: diva2:1384862
Forskningsfinansiär
Västerbottens läns landstingTillgänglig från: 2020-01-11 Skapad: 2020-01-11 Senast uppdaterad: 2023-03-24Bibliografiskt granskad
Ingår i avhandling
1. Functional brain imaging of sensorimotor dysfunction and restoration: investigations of discomplete spinal cord injury and deep brain stimulation for essential tremor
Öppna denna publikation i ny flik eller fönster >>Functional brain imaging of sensorimotor dysfunction and restoration: investigations of discomplete spinal cord injury and deep brain stimulation for essential tremor
2022 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Alternativ titel[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.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2022. s. 136
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2194
Nyckelord
Sensorimotor control, fMRI, discomplete spinal cord injury, essential tremor, deep brain stimulation, cerebello-thalamo-cerebral circuit
Nationell ämneskategori
Neurovetenskaper Neurologi
Forskningsämne
fysiologi; neurokirurgi; neurologi; rehabiliteringsmedicin
Identifikatorer
urn:nbn:se:umu:diva-197840 (URN)978-91-7855-837-7 (ISBN)978-91-7855-838-4 (ISBN)
Disputation
2022-08-29, Hörsal Betula, Målpunkt L, Norrlands universitetssjukhus, Umeå, 09:00 (Engelska)
Opponent
Handledare
Tillgänglig från: 2022-08-16 Skapad: 2022-07-14 Senast uppdaterad: 2022-08-09Bibliografiskt granskad

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Awad, AmarBlomstedt, PatricWestling, GöranEriksson, Johan

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