title: Hyperventilation in Patients With Focal Epilepsy: Electromagnetic Tomography, Functional Connectivity and Graph Theory - A Possible Tool in Epilepsy Diagnosis?
abstract: OBJECTIVE
  Hyperventilation (HV) is a commonly used electroencephalogram activation method.
  
  
  METHODS
  We analyzed EEG recordings in 22 normal subjects and 22 patients with focal epilepsy of unknown cause. We selected segments before (PRE), during (HYPER), and 5 minutes after (POST) HV. To analyze the neural generators of EEG signal, we used standard low-resolution electromagnetic tomography (sLORETA software). We then computed EEG lagged coherence, an index of functional connectivity, between 19 regions of interest. A weighted graph was built for each band in every subject, and characteristic path length (L) and clustering coefficient (C) have been computed. Statistical comparisons were performed by means of analysis of variance (Group X Condition X Band) for mean lagged coherence, L and C.
  
  
  RESULTS
  Hyperventilation significantly increases EEG neural generators (P < 0.001); the effect is particularly evident in cingulate cortex. Functional connectivity was increased by HV in delta, theta, alpha, and beta bands in the Epileptic group (P < 0.01) and only in theta band in Control group. Intergroup analysis of mean lagged coherence, C and L, showed significant differences for Group (P < 0.001), Condition (P < 0.001), and Band (P < 0.001). Analysis of variance for L also showed significant interactions: Group X Condition (P = 0.003) and Group X Band (P < 0.001).
  
  
  CONCLUSIONS
  In our relatively small group of epileptic patients, HV is associated with activation of cingulate cortex; moreover, it modifies brain connectivity. The significant differences in mean lagged coherence, path length, and clustering coefficient permit to hypothesize that this activation method leads to different brain connectivity patterns in patients with epilepsy when compared with normal subjects. If confirmed by other studies involving larger populations, this analysis could become a diagnostic tool in epilepsy.
authors.affiliation: *Institute of Neurosurgery, Università Cattolica del Sacro Cuore, Rome, Italy; †Department of Geriatrics, Neuroscience and Orthopedics, Institute of Neurology, Università Cattolica del Sacro Cuore, Rome, Italy; ‡Institute of Neurology, Istituto Auxologico Italiano, Milan, Italy; §Clinica Luganese, Lugano, Switzerland; and ‖Child and Adolescent Unit, Department of Basic Medical Sciences, Neurosciences and Sense Organs, Università degli Studi Aldo Moro, Bari, Italy.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mazzucchi
authors.forename: Catello
authors.initials: C
authors.lastname: Vollono
authors.forename: Anna
authors.initials: A
authors.lastname: Losurdo
authors.forename: Elisa
authors.initials: E
authors.lastname: Testani
authors.forename: Valentina
authors.initials: V
authors.lastname: Gnoni
authors.forename: Chiara
authors.initials: C
authors.lastname: Di Blasi
authors.forename: Nadia M
authors.initials: NM
authors.lastname: Giannantoni
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lapenta
authors.forename: Valerio
authors.initials: V
authors.lastname: Brunetti
authors.forename: Giacomo
authors.initials: G
authors.lastname: Della Marca
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D004569:Electroencephalography / Q000379:methods*; D004828:Epilepsies, Partial / Q000175:diagnosis* / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006985:Hyperventilation / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology; D012815:Signal Processing, Computer-Assisted; D012984:Software; D014054:Tomography / Q000379:methods*; D055815:Young Adult