Studio della “Connettività Funzionale” con Risonanza Magnetica

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
1Dept.
of Bioimages and Radiological Sciences
Catholic University of ROME – ITALY
2I.T.A.B.
– Dept. of Neurosciences
“G. d’Annunzio” University – CHIETI - ITALY
Mail to: [email protected]
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)
1van
Rijckevorsel 2006; 2Wheless 2002; 3Davie 1991
4Bràzdil 2005; 5Springer 1999
6Biswal
1995;
Purposes
• To evaluate hemispheric language lateralization during a conventional verbgeneration 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. 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
Cryptogenetic
DNT
AVM
Micropoligyrya
4
4
1
1
1
MTS
DNT
Cavernoma
Cortical Dysplasia
Micropoligyrya
6
2
1
1
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-IVR) 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.)
Subjects and Methods – 2
FC 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 Maps
Random Effect Analysis, P < .05, FDR-corrected)
Pair-Wise Functional Connectivity Plots and Matrices
(two-tailed t-test P < .01)
Results – 1
“Conventional” Task-Evoked Experiment
f-MRI Language Activations
L
R
• Taken together, all patients (22) showed
more complex and bilateral language
activations compared to controls:
mean LI = 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)
Results – 2
FC Pair-Wise analysis
- 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.
Results – 3
FC Voxel-Wise Statistical Maps
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
R
the Posterior Cingulate Cortex (PCC) only
in the patient group
Random Effect Analysis; p < .05 corrected for multiple
comparisons with FDR. Only clusters >5mm2 are
shown.
Panel A: Controls
Panel B: Patients
Results – 4
Separated Patients Groups according to the EF side
Patients with
L – Epileptogenic Focus
Patients with
R – Epileptigenic Focus
Verbal – IQ scores
r = 0.7; P < .0 5
Left Intra-hemispheric FC (z-scores)
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.
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 – 4
Correlation with Post-Operative Language Performance
• 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
r = -0.6; P < .05
Inter-hemispheric FC (z-scores)
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.
Thank you!