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1 Dept. of Bioimages and Radiological Sciences Catholic University of ROME – ITALY

Functional Connectivity MRI (FC-MRI) of the Language Network in patients with drug-resistant Epilepsy Pravatà E 1 , Sestieri C 2 , Mantini D 2 , Briganti C 2 , Colicchio G 1 , Colosimo C 1 , Tartaro A 2 , Romani GL 2 , Caulo M 2. 1 Dept. of Bioimages and Radiological Sciences

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1 Dept. of Bioimages and Radiological Sciences Catholic University of ROME – ITALY

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  1. FunctionalConnectivity MRI (FC-MRI) of the Language Network in patientswithdrug-resistantEpilepsy PravatàE1, Sestieri C2, Mantini D2, Briganti C2, Colicchio G1, Colosimo C1, Tartaro A2 ,Romani GL2, Caulo M2 1Dept. ofBioimages and RadiologicalSciences CatholicUniversityofROME – ITALY 2I.T.A.B. – Dept. ofNeurosciences “G. d’Annunzio” University – CHIETI - ITALY Mail to: emanuele.pravata@gmail.com

  2. Introduction Epilepsy, Language and Functional Connectivity • “Epilepsyis more thanseizures”(1): Subtle linguistic dysfunctions -especially receptive language- in up to a third of adults with chronic Epilepsy(2,3) • In epileptic patients, different patterns of language activation and lateralization at f-MRI studies compared to normal subjects(4,5) • Functional Connectivity (FC) – MRI investigates cortical connectivity by evaluating correlations of spontaneous low-frequency BOLD signal fluctuations between distant regions(6) 6Biswal 1995; 1van Rijckevorsel 2006; 2Wheless 2002; 3Davie 1991 4Bràzdil 2005; 5Springer 1999

  3. Purposes • To evaluate hemispheric language lateralization during a conventional verb-generation task experiment in patients with drug-resistant epilepsy and healthy subjects • To investigate the pattern of FC across six language-related “seeding” regions in both hemispheres (IFG, T1p, T2ml) already identified in previous works1 • To correlate FC-MRI data to patients’ verbal-Intelligence Quotients (vIQs) scores • 1 : • Heim S. NeurosciLett 2002 • Seghier ML Hum Brain Mapp 2004 • Luke KK. Hum Brain Mapp 2002 • Vigneau M. Neuroimage 2006

  4. Subjects and Methods - 1 • Drug-Resistant Epilepsy (and Epileptogenic Focus side) diagnoses based on EEG recordings, MRI examination and clinical assessment. • Only Pts with lesions not having a tendency to grow nor to broadly alter the normal anatomy and distant from cortical regions for speech • The control group included 12 healthy right-handed*, age- and sex-matched subjects (mean age = 35) • 17/22 Patients’ verbal-IQ derived from the Wechsler Adult Intelligence Scale IV- Revised (WAIS-IV-R) test for language • Data were acquired on 1.5T systems (Magnetom Vision, Siemens, Erlangen, Germany and Achieva, Philips Medical Systems, Best, the Netherlands) *As from the Edinburgh Handedness Inventory test (Italian ver.)

  5. Subjects and Methods – 2 FC Analysis • FCtime-course extracted from experiment’s BOLD time-course according to the procedures described in Fox et al. (2005) and Fair et al. (2006): • Band-pass filtering between 0.009 and 0.08 Hz; • Regression of: deterministic task-evoked components, white matter and ventricle signals, and motion parameters. 2. Pair-Wise and Voxel-Wise analyses using Pearson’s correlation coefficients (r) togenerate: - FC Diagrams and Matrices between LN seeding regions in pairs - FC Maps from individual seeds, covering all the acquisition volume Voxel-WiseFunctionalConnectivityMaps RandomEffectAnalysis, P < .05, FDR-corrected) Pair-WiseFunctionalConnectivityPlots and Matrices (two-tailed t-test P < .01)

  6. Results – 1 “Conventional” Task-EvokedExperiment f-MRI Language Activations L R • Takentogether, allpatients (22) showed more complexand bilaterallanguageactivationscomparedtocontrols: • meanLI = 0.23 vs. 0.43; P < .05 (P < .01, FDR-corrected for multiple comparisons. Only clusters >10 mm2 are represented) • … however • Only LE patients (11) had significant less lateralized language activations compared to controls: (Mean LI=0.11 vs. 0.43; P < .05)

  7. Results – 2 FC Pair-Wiseanalysis - 4 links Plots (upper row) show significant correlations by segments of variable thickness. These are further represented in the Ccolor-coded matrices (lower row), ranging from white (z= 0) to dark red (z = 0.7). Only correlations significant at P < .01 are shown. Patients’ significantly reduced FC links at P < .01 are shown in black lines between the nodes.

  8. Results – 3 FC Voxel-WiseStatisticalMaps Seed: Left – T1p • Controls demonstrate that the L-T1p region showed correlationalmost exclusively with other regions of the LN • Patients suffered significant reduction of connectivity between L-T1p and other LN regions • L-T1p was functionally connected with the Posterior Cingulate Cortex (PCC) only in the patient group R RandomEffectAnalysis; p < .05 correctedfor multiple comparisonswith FDR. Onlyclusters >5mm2 are shown. Panel A: Controls Panel B: Patients

  9. Results – 4 SeparatedPatientsGroupsaccordingto the EF side Patientswith L – Epileptogenic Focus Patientswith R – Epileptigenic Focus r = 0.7; P < .0 5 Verbal – IQ scores LeftIntra-hemispheric FC (z-scores) L – Intra-hemispheric FC Connectivity plots show statistically significant correlations by segments of variable thickness according to the Pearson’s coefficients values. Only correlations significant at P < .05 are shown.

  10. Conclusions -1 • Wefoundthatregardless the EF side, FC wasstronglyreduced in the dominanthemisphere and in particular in the T1p region, demonstrating the centralroleofWernicke’s area in the LN • In patientswithleft EF, the combinationofreducedlanguagelateralizationand FC in the dominanthemisphere,correlatedwith the reductionofpatients’ linguistic performance • The connectivitylinksto the DMN suggest the presenceofplasticitychangesdue toEpilepsyalsoinvolvingareasnotrelatedtolanguage • The evaluation of FC underlying task-evoked activations may provide better understanding of the functional modification induced by epilepsy.

  11. Results – 4 Correlationwith Post-Operative Language Performance r = -0.6; P < .05 • From these partial results, it seems that a stronger FC between the hemispheres before surgery might be unfavourable for post-operative performance. Verbal – IQ scores Inter-hemisphericFC (z-scores) Pre-OperativeInter-hemispheric FC 10 Patientsweretestedagainat least 6 monthsaftersurgery, and allofthemhadno seizuresand hadno change in medicaltherapy.

  12. Thank you!

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