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Evaluation of the effects of DBS in the caudal Zona incerta on brain activity during a working memory task in patients with essential tremor
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.ORCID-id: 0000-0002-7063-9710
Umeå universitet, Medicinska fakulteten, Umeå centrum för funktionell hjärnavbildning (UFBI). Umeå universitet, Medicinska fakulteten, Institutionen för integrativ medicinsk biologi (IMB), Fysiologi.
Department of Psychology, Lund University, Lund, Sweden.
Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Neurovetenskaper.
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2023 (Engelska)Ingår i: Neuroimage: Reports, ISSN 2666-9560, Vol. 3, nr 4, artikel-id 100193Artikel i tidskrift (Refereegranskat) 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.

Ort, förlag, år, upplaga, sidor
Elsevier, 2023. Vol. 3, nr 4, artikel-id 100193
Nyckelord [en]
Deep brain stimulation, Essential tremor, Working memory, fMRI
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
neurologi
Identifikatorer
URN: urn:nbn:se:umu:diva-204363DOI: 10.1016/j.ynirp.2023.100193Scopus ID: 2-s2.0-85175237822OAI: oai:DiVA.org:umu-204363DiVA, id: diva2:1733530
Forskningsfinansiär
Vetenskapsrådet
Anmärkning

Originally included in thesis in manuscript form.

Tillgänglig från: 2023-02-02 Skapad: 2023-02-02 Senast uppdaterad: 2023-11-09Bibliografiskt granskad
Ingår i avhandling
1. Cognitive effects of deep brain stimulation: focus on caudal zona incerta for essential tremor and Parkinson´s disease, and on bed nucleus of stria terminalis for obsessive compulsive disorder
Öppna denna publikation i ny flik eller fönster >>Cognitive effects of deep brain stimulation: focus on caudal zona incerta for essential tremor and Parkinson´s disease, and on bed nucleus of stria terminalis for obsessive compulsive disorder
2023 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Alternativ titel[sv]
Kognitiva effekter av deep brain stimulation (djup hjärnstimulering) : fokus på caudal zona incerta vid essentiell tremor och Parkinsons sjukdom, samt på bed nucleus stria terminalis vid tvångssyndrom
Abstract [en]

Preserved cognition is an important determinant for perceived Quality of Life (QoL) and has been found to be essential in order to translate improvements in primary symptoms following Deep Brain Stimulation (DBS) into activities of daily living that drive QoL. Therefore, it is important to evaluate not only the clinical improvement, but also the cognitive impact of DBS.

The aim of this thesis was to evaluate the cognitive effects of DBS in a new target, the caudal Zona incerta (cZi), which has shown promising results in patients with both Parkinson’s Disease (PD) and Essential Tremor (ET). Given that this is a novel target, the effects on cognition were lacking in the literature. In the same manner, the cognitive effects in patients with Obsessive-Compulsive Disorder (OCD) receiving DBS in the Bed Nucleus of Stria Terminalis (BNST) lacked long-term follow-up.

The main findings from the studies included in this thesis, suggest that DBS in the cZi in patients with PD and ET, and in the BNST in patients with OCD, does not generate any major cognitive effects and can be considered safe from a cognitive perspective.However, subtle effects involving aspects of executive function may be present following cZi DBS in patients with PD. Significant results concerned primarily a decrease in selective attention and aspects of inhibition. cZi DBS in patients with ET generated fewer cognitive effects, including a decrease in semantic verbal fluency 12 months after DBS in the cZi. fMRI results evaluating the effects of cZi DBS on brain activity during a working memory task, did not show any significant changes when DBS was ON or OFF. This study also revealed a significant Task-x-DBS interaction, with faster response times during DBS ON relative to DBS OFF for the more cognitively demanding “manipulation” task. In OCD patients with BNST DBS, improved results on the Color-Word Inhibition/switching subtest were found, indicating a possible improvement in cognitive flexibility. However, there was a decrease of performance in visuo-spatial learning at 12 months after surgery.

The studies in patients with PD and ET were the first to report comprehensive neuropsychological data regarding cZi DBS. The fMRI study was the first in patients with ET treated with cZi DBS, focusing on cognitive effects during a working memory task in on/off DBS conditions. The OCD study was the first to report long-term data on cognitive effects after BNST DBS. By showing that DBS in these targets does not produce any major cognitive side effects, valuable knowledge in terms of safety has been added. This will hopefully contribute to increased treatment options in DBS.

Ort, förlag, år, upplaga, sidor
Umeå: Umeå University, 2023. s. 79
Serie
Umeå University medical dissertations, ISSN 0346-6612 ; 2226
Nyckelord
Deep brain stimulation. Neuropsychology. Cognition. Parkinson’s disease. Essential tremor. Obsessive-compulsive disorder. Caudal zona incerta. Bed nucleus of stria terminalis. Functional MRI.
Nationell ämneskategori
Neurovetenskaper
Forskningsämne
neurologi
Identifikatorer
urn:nbn:se:umu:diva-204361 (URN)978-91-7855-995-4 (ISBN)978-91-7855-996-1 (ISBN)
Disputation
2023-03-03, Hörsal D, målplan T, plan 9, Norrlands universitetssjukhus, Umeå, 09:00 (Engelska)
Opponent
Handledare
Anmärkning

Oregelbunden paginering / Various pagings.

Tillgänglig från: 2023-02-10 Skapad: 2023-02-02 Senast uppdaterad: 2023-02-08Bibliografiskt granskad

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