title: Interhemispheric connectivity in amyotrophic lateral sclerosis: A near-infrared spectroscopy and diffusion tensor imaging study.
abstract: Aim of the present study was to investigate potential impairment of non-motor areas in amyotrophic lateral sclerosis (ALS) using near-infrared spectroscopy (NIRS) and diffusion tensor imaging (DTI). In particular, we evaluated whether homotopic resting-state functional connectivity (rs-FC) of non-motor associated cortical areas correlates with clinical parameters and disease-specific degeneration of the corpus callosum (CC) in ALS.
  
  
  
  Interhemispheric homotopic rs-FC was assessed in 31 patients and 30 healthy controls (HCs) for 8 cortical sites, from prefrontal to occipital cortex, using NIRS. DTI was performed in a subgroup of 21 patients. All patients were evaluated for cognitive dysfunction in the executive, memory, and visuospatial domains.
  
  
  
  ALS patients displayed an altered spatial pattern of correlation between homotopic rs-FC values when compared to HCs (p= 0.000013). In patients without executive dysfunction a strong correlation existed between the rate of motor decline and homotopic rs-FC of the anterior temporal lobes (ATLs) (ρ = - 0.85,p= 0.0004). Furthermore, antero-temporal homotopic rs-FC correlated with fractional anisotropy in the central corpus callosum (CC), corticospinal tracts (CSTs), and forceps minor as determined by DTI (p< 0.05).
  
  
  
  The present study further supports involvement of non-motor areas in ALS. Our results render homotopic rs-FC as assessed by NIRS a potential clinical marker for disease progression rate in ALS patients without executive dysfunction and a potential anatomical marker for ALS-specific degeneration of the CC and CSTs.
authors.affiliation: Clinic for Neurology and Stereotactic Neurosurgery, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany; Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118 Magdeburg, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kopitzki
authors.affiliation: Clinic for Neurology and Stereotactic Neurosurgery, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Oldag
authors.affiliation: Clinic for Neurology and Stereotactic Neurosurgery, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Sweeney-Reed
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Judith
authors.initials: J
authors.lastname: Machts
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Veit
authors.affiliation: Clinic for Neurology and Stereotactic Neurosurgery, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Jörn
authors.initials: J
authors.lastname: Kaufmann
authors.affiliation: Clinic for Neurology and Stereotactic Neurosurgery, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany; Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Hermann
authors.initials: H
authors.lastname: Hinrichs
authors.affiliation: Clinic for Neurology and Stereotactic Neurosurgery, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany; Leibniz Institute for Neurobiology, Brenneckestrasse 6, 39118 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Hans-Jochen
authors.initials: HJ
authors.lastname: Heinze
authors.affiliation: Department of Neurology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Katja
authors.initials: K
authors.lastname: Kollewe
authors.affiliation: Department of Neurology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Petri
authors.affiliation: Department of Neurology, Luebeck University, Ratzeburger Allee 160, 23538 Luebeck, Germany.
authors.forename: Bahram
authors.initials: B
authors.lastname: Mohammadi
authors.affiliation: Department of Neurology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Dengler
authors.affiliation: Clinic for Neurology and Stereotactic Neurosurgery, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany; NEUROLOGY MOVES, Bismarckstrasse 45-47, 10627 Berlin, Germany.
authors.forename: Andreas R
authors.initials: AR
authors.lastname: Kupsch
authors.affiliation: Clinic for Neurology and Stereotactic Neurosurgery, Otto-von-Guericke University, Leipziger Strasse 44, 39120 Magdeburg, Germany; German Center for Neurodegenerative Diseases (DZNE), Leipziger Strasse 44, 39120 Magdeburg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Vielhaber
mesh_terms: D000368:Aged; D000690:Amyotrophic Lateral Sclerosis / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D003430:Cross-Sectional Studies; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D019265:Spectroscopy, Near-Infrared; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology
keywords: AC, anterior commissure; ALS, amyotrophic lateral sclerosis; ALS-EX, ALS with executive impairment; ALS-NECI, ALS with non-executive cognitive impairment; ALSFRS-R, revised ALS functional rating scale; ATL, anterior temporal lobe; Amyotrophic lateral sclerosis; CC, corpus callosum; CST, corticospinal tract; Corpus callosum; DD, disease duration; DPR, disease progression rate; DTI, diffusion tensor imaging; Diffusion tensor imaging; FA, fractional anisotropy; FTD, frontotemporal dementia; HC, healthy control; Hb, hemoglobin; Interhemispheric connectivity; NIRS, near-infrared spectroscopy; Near-infrared spectroscopy; TBSS, tract based spatial statistics; WM, white matter; fMRI, functional magnetic resonance imaging; pALS, pure ALS no cognitive impairment; rs-FC, resting-state functional connectivity; rs-fNIRS, resting-state functional NIRS