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@ARTICLE{Holtbernd:893243,
      author       = {Holtbernd, Florian and Shah, N. Jon},
      title        = {{I}maging the {P}athophysiology of {E}ssential
                      {T}remor—{A} {S}ystematic {R}eview},
      journal      = {Frontiers in neurology},
      volume       = {12},
      issn         = {1664-2295},
      address      = {Lausanne},
      publisher    = {Frontiers Research Foundation},
      reportid     = {FZJ-2021-02643},
      pages        = {680254},
      year         = {2021},
      abstract     = {Background: The pathophysiology underlying essential tremor
                      (ET) still is poorly understood. Recent research suggests a
                      pivotal role of the cerebellum in tremor genesis, and an
                      ongoing controversy remains as to whether ET constitutes a
                      neurodegenerative disorder. In addition, mounting evidence
                      indicates that alterations in the gamma-aminobutyric acid
                      neurotransmitter system are involved in ET pathophysiology.
                      Here, we systematically review structural, functional, and
                      metabolic neuroimaging studies and discuss current concepts
                      of ET pathophysiology from an imaging perspective.Methods:
                      We conducted a PubMed and Scopus search from 1966 up to
                      December 2020, entering essential tremor in combination with
                      any of the following search terms and their corresponding
                      abbreviations: positron emission tomography (PET),
                      single-photon emission computed tomography (SPECT), magnetic
                      resonance imaging (MRI), magnetic resonance spectroscopy
                      (MRS), and gamma-aminobutyric acid (GABA).Results: Altered
                      functional connectivity in the cerebellum and
                      cerebello-thalamico-cortical circuitry is a prevalent
                      finding in functional imaging studies. Reports from
                      structural imaging studies are less consistent, and there is
                      no clear evidence for cerebellar neurodegeneration. However,
                      diffusion tensor imaging robustly points toward
                      microstructural cerebellar changes. Radiotracer imaging
                      suggests that the dopaminergic axis is largely preserved in
                      ET. Similarly, measurements of nigral iron content and
                      neuromelanin are unremarkable in most studies; this is in
                      contrast to Parkinson's disease (PD). PET and MRS studies
                      provide limited evidence for cerebellar and thalamic
                      GABAergic dysfunction.Conclusions: There is robust evidence
                      indicating that the cerebellum plays a key role within a
                      multiple oscillator tremor network which underlies tremor
                      genesis. However, whether cerebellar dysfunction relies on a
                      neurodegenerative process remains unclear. Dopaminergic and
                      iron imaging do not suggest a substantial overlap of ET with
                      PD pathophysiology. There is limited evidence for
                      alterations of the GABAergic neurotransmitter system in ET.
                      The clinical, demographical, and genetic heterogeneity of ET
                      translates into neuroimaging and likely explains the various
                      inconsistencies reported.},
      cin          = {INM-4 / INM-11 / JARA-BRAIN},
      ddc          = {610},
      cid          = {I:(DE-Juel1)INM-4-20090406 / I:(DE-Juel1)INM-11-20170113 /
                      I:(DE-Juel1)VDB1046},
      pnm          = {525 - Decoding Brain Organization and Dysfunction
                      (POF4-525)},
      pid          = {G:(DE-HGF)POF4-525},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {34220687},
      UT           = {WOS:000668112300001},
      doi          = {10.3389/fneur.2021.680254},
      url          = {https://juser.fz-juelich.de/record/893243},
}