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@ARTICLE{Freri:283047,
      author       = {Freri, Fabiola and Spinelli, Edoardo Gioele and Canu, Elisa
                      and Basaia, Silvia and Castelnovo, Veronica and Müller,
                      Hans-Peter and Kassubek, Jan and Ludolph, Albert C and
                      Krishnamurthy, Sruthi Sankari and Roselli, Francesco and
                      Filippi, Massimo and Agosta, Federica},
      title        = {{U}ncovering hypothalamic network disruption in {ALS}.},
      journal      = {Journal of neurology},
      volume       = {273},
      number       = {1},
      issn         = {0367-004X},
      address      = {[Darmstadt]},
      publisher    = {Steinkopff},
      reportid     = {DZNE-2025-01454},
      pages        = {37},
      year         = {2026},
      abstract     = {Structural MRI studies have shown hypothalamic atrophy and
                      altered white matter (WM) connectivity in amyotrophic
                      lateral sclerosis (ALS), as a possible substrate of
                      hypermetabolism in this condition. However, hypothalamic
                      functional connectivity and its association with clinical
                      features in ALS remain unclear. This study explored
                      hypothalamic resting-state functional connectivity (RS-FC)
                      in ALS patients compared to controls and its relationship
                      with disease severity defined by the ALS Functional Rating
                      Scale (ALSFRS-r), body mass index (BMI), disease duration,
                      progression rate, survival, hypothalamic volume, and WM
                      integrity.Seventy-one ALS patients and 39 healthy controls
                      underwent structural and RS functional MRI. The bilateral
                      hypothalamus was segmented, and a seed-based RS-FC analysis
                      was performed. Group differences in hypothalamic RS-FC and
                      their correlations with ALSFRS-r scores, BMI, disease
                      duration, progression rate, survival, hypothalamic volume,
                      and WM integrity were assessed. Tract-based spatial
                      statistics was performed to estimate the correlation between
                      WM damage in ALS and hypothalamic RS-FC.ALS patients showed
                      increased hypothalamic RS-FC with caudate nuclei compared to
                      controls. Additionally, greater disease severity correlated
                      with increased hypothalamic RS-FC with the caudate nuclei
                      and orbitofrontal cortex. Hypothalamic RS-FC mean values
                      also associated with FA in the genu of corpus callosum and
                      forceps minor and disease progression rate. No significant
                      correlations were observed with other clinical
                      features.These findings support hypothalamic alterations in
                      ALS. Early detection of hypothalamic changes could be useful
                      in prognostic stratification and evaluating intervention
                      effects.},
      keywords     = {Humans / Amyotrophic Lateral Sclerosis: diagnostic imaging
                      / Amyotrophic Lateral Sclerosis: physiopathology /
                      Amyotrophic Lateral Sclerosis: pathology / Female / Male /
                      Middle Aged / Hypothalamus: diagnostic imaging /
                      Hypothalamus: physiopathology / Hypothalamus: pathology /
                      Magnetic Resonance Imaging / Aged / Adult / White Matter:
                      diagnostic imaging / White Matter: pathology / Nerve Net:
                      diagnostic imaging / Nerve Net: physiopathology / Disease
                      Progression / Connectome / Amyotrophic lateral sclerosis
                      (Other) / Functional connectivity (Other) / Hypermetabolism
                      (Other) / Hypothalamus (Other) / MRI (Other)},
      cin          = {Clinical Study Center (Ulm) / AG Roselli},
      ddc          = {610},
      cid          = {I:(DE-2719)5000077 / I:(DE-2719)1910001},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41428120},
      pmc          = {pmc:PMC12722382},
      doi          = {10.1007/s00415-025-13574-3},
      url          = {https://pub.dzne.de/record/283047},
}