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Evidence for cognitive resource imbalance in adolescents with narcolepsy
Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).
Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV).ORCID iD: 0000-0002-7809-2481
Linköping University, Department of Behavioural Sciences and Learning, Disability Research. Linköping University, Faculty of Arts and Sciences. (Linnaeus Center HEAD)
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2018 (English)In: Brain Imaging and Behavior, ISSN 1931-7557, E-ISSN 1931-7565, Vol. 12, no 2, p. 411-424Article in journal (Refereed) Published
Abstract [en]

The study investigated brain activity changes during performance of a verbal working memory task in a population of adolescents with narcolepsy. Seventeen narcolepsy patients and twenty healthy controls performed a verbal working memory task during simultaneous fMRI and EEG acquisition. All subjects also underwent MRS to measure GABA and Glutamate concentrations in the medial prefrontal cortex. Activation levels in the default mode network and left middle frontal gyrus were examined to investigate whether narcolepsy is characterized by an imbalance in cognitive resources. Significantly increased deactivation within the default mode network during task performance was observed for the narcolepsy patients for both the encoding and recognition phases of the task. No evidence for task performance deficits or reduced activation within the left middle frontal gyrus was noted for the narcolepsy patients. Correlation analyses between the spectroscopy and fMRI data indicated that deactivation of the anterior aspect of the default mode in narcolepsy patients correlated more with increased concentrations of Glutamate and decreased concentrations of GABA. In contrast, deactivation in the default mode was correlated with increased concentrations of GABA and decreased concentrations of Glutamate in controls. The results suggested that narcolepsy is not characterized by a deficit in working memory but rather an imbalance of cognitive resources in favor of monitoring and maintaining attention over actual task performance. This points towards dysregulation within the sustained attention system being the origin behind self-reported cognitive difficulties in narcolepsy.

Place, publisher, year, edition, pages
Springer-Verlag New York, 2018. Vol. 12, no 2, p. 411-424
Keywords [en]
EEG, GABA, MRS, Narcolepsy, Working memory, fMRI
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:liu:diva-145535DOI: 10.1007/s11682-017-9706-yISI: 000429029000011PubMedID: 28321606Scopus ID: 2-s2.0-85015625386OAI: oai:DiVA.org:liu-145535DiVA, id: diva2:1187615
Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2019-01-04Bibliographically approved
In thesis
1. Brain Networks and Dynamics in Narcolepsy
Open this publication in new window or tab >>Brain Networks and Dynamics in Narcolepsy
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Narcolepsy is a chronic sleep disorder, characterised by excessive daytime sleepiness with frequent uncontrollable sleep attacks. In addition to sleeprelated problems, changes in cognition have also been observed in patients with narcolepsy and has been linked to the loss of Orexin-A in a number of studies. Results from previous functional and structural neuroimaging studies would suggest that the loss of Orexin-A has numerous downstream effects in terms of both resting state glucose metabolism and perfusion and reduction in cortical grey matter.

Specifically, studies investigating narcolepsy with positron emission tomography (PET) and single photon emission computed tomography (SPECT) have observed aberrant perfusion and glucose metabolism in the hypothalamus and thalamus, as well as in prefrontal cortex. A very recent PET study in a large cohort of adolescents with type 1 narcolepsy further observed that the hypoand hypermetabolism in many of these cortico-frontal and subcortical brain regions also exhibited significant correlations with performance on a number of neurocognitive tests. These findings parallel those found in structural neuroimaging studies, where a reduction of cortical grey matter in frontotemporal areas has been observed.

The Aim of this thesis was to investigate mechanisms and aetiology behind the symptoms in narcolepsy through the application of different neuroimaging techniques. I present in this thesis evidence supporting that the complaints about subjective memory deficits in narcolepsy are related to a misallocation of resources.

I further describe how this has its seat in defective default mode network activation, possibly involving alterations to GABA and Glutamate signaling. In addition to this, I present our findings of a structural deviation in an area of the brainstem previously not described in the aetiology of narcolepsy.

This finding may have implications for further understanding the aetiology of the disease and the specific neuronal populations involved.

In addition to this, I show evidence from adipose tissue measurements in specific compartments, confirming that weight gain in narcolepsy is characterized by centrally located weight gain and may be specifically related to OX changes, but maybe not brown adipose tissue volume.

The findings presented in this thesis provides new insights to the pathophysiology of narcolepsy beyond the well-known depletion of OX producing neurons in the hypothalamus.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 54
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 1651
National Category
Neurosciences Radiology, Nuclear Medicine and Medical Imaging Neurology Physiology
Identifiers
urn:nbn:se:liu:diva-153629 (URN)10.3384/diss.diva-153629 (DOI)9789176851814 (ISBN)
Public defence
2019-01-25, Hugo Theorells sal, Campus US, Linköping, 09:15 (English)
Opponent
Supervisors
Available from: 2019-01-04 Created: 2019-01-04 Last updated: 2019-01-07Bibliographically approved

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Drissi, Natasha MoralesTapper, SofieWretman, AnnaLandtblom, Anne-MarieKarlsson, ThomasLundberg, PeterEngström, Maria

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Witt, Suzanne TDrissi, Natasha MoralesTapper, SofieWretman, AnnaLandtblom, Anne-MarieKarlsson, ThomasLundberg, PeterEngström, Maria
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Faculty of Medicine and Health SciencesCenter for Medical Image Science and Visualization (CMIV)Division of Radiological SciencesDisability ResearchFaculty of Arts and SciencesDivision of Neuro and Inflammation ScienceDepartment of NeurologyDepartment of Radiation Physics
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