1Dept. of Bioimages and Radiological SciencesCatholic University of ROME – ITALY

2I.T.A.B. – Dept. of Neurosciences“G. d’Annunzio” University – CHIETI - ITALY

Mail to: emanuele.pravata@gmail.com

Functional Connectivity MRI (FC-MRI) of the Language Network in patients with drug-resistant Epilepsy

Pravatà E1, Sestieri C2, Mantini D2, Briganti C2, Colicchio G1, Colosimo C1, Tartaro A2 , Romani GL2, Caulo M2

1van Rijckevorsel 2006; 2Wheless 2002; 3Davie 19914Bràzdil 2005; 5Springer 1999

Introduction Epilepsy, Language and Functional Connectivity

• “Epilepsy is more than seizures”(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;

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)

scores1 : • Heim S. Neurosci Lett 2002• Seghier ML Hum Brain Mapp 2004• Luke KK. Hum Brain Mapp 2002• Vigneau M. Neuroimage 2006

Subjects and Methods - 1

22 Right-handed* Patients, (Age: 30 ± 10; range 16-51), with Drug-Resistant Epilepsy

Right-Epileptogenic focus (RE) (N = 11) Left-Epileptogenic focus (RE) (N = 11)MTS 4 MTS 6Cryptogenetic 4 DNT 2DNT 1 Cavernoma 1AVM 1 Cortical Dysplasia 1Micropoligyrya 1 Micropoligyrya 1

*As from the Edinburgh Handedness Inventory test (Italian ver.)

• 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)

Subjects and Methods – 2FC Analysis

1. FC time-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) to generate:

- FC Diagrams and Matrices between LN seeding regions in pairs - FC Maps from individual seeds, covering all the acquisition volume

Voxel-Wise Functional Connectivity MapsRandom Effect Analysis, P < .05, FDR-corrected) Pair-Wise Functional Connectivity Plots and Matrices

(two-tailed t-test P < .01)

• Taken together, all patients (22) showed more complex and bilateral language activations compared to controls:

mean LI = 0.23 vs. 0.43; P < .05

Results – 1“Conventional” Task-Evoked Experiment

f-MRI Language Activations

… however

• Only LE patients (11) had significant less lateralized language activations compared to controls: (Mean LI=0.11 vs. 0.43; P < .05)

L R

(P < .01, FDR-corrected for multiple comparisons. Only clusters >10 mm2 are represented)

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.

Results – 2FC Pair-Wise analysis

Patients’ significantly reduced FC links at P < .01 are shown in black lines between the nodes.

- 4 links

Random Effect Analysis; p < .05 corrected for multiple comparisons with FDR. Only clusters >5mm2 are shown.

Panel A: ControlsPanel B: Patients

Results – 3FC Voxel-Wise Statistical Maps

R

Seed: Left – T1p

• Controls demonstrate that the L-T1p region showed correlation almost 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

Results – 4Separated Patients Groups according to the EF side

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.

Patients with L – Epileptogenic Focus

Patients withR – Epileptigenic Focus

Verb

al –

IQ s

core

s

L – Intra-hemispheric FC

Left Intra-hemispheric FC (z-scores)

r = 0.7; P < .0 5

Conclusions -1

• We found that regardless the EF side, FC was strongly reduced in the dominant hemisphere and in particular in the T1p region, demonstrating the central role of Wernicke’s area in the LN

• In patients with left EF, the combination of reduced language lateralization and FC in the dominant hemisphere, correlated with the reduction of patients’ linguistic performance

• The connectivity links to the DMN suggest the presence of plasticity changes due to Epilepsy also involving areas not related to language

• The evaluation of FC underlying task-evoked activations may provide better understanding of the functional modification induced by epilepsy.

Results – 4Correlation with Post-Operative Language Performance

10 Patients were tested again at least 6 months after surgery, and all of them had no seizures and had no change in medical therapy.

Verb

al –

IQ s

core

s

Pre-Operative Inter-hemispheric FC

Inter-hemispheric FC (z-scores)

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.

Thank you!