Epilepsia, 47(3):589–592, 2006 Blackwell Publishing, Inc. C 2006 International League Against Epilepsy
Language and Motor f MRI Activation in Polymicrogyric Cortex ∗ David Araujo, †Draulio B. de Araujo, ∗ Octavio M. Pontes-Neto, ∗ Sara Escorsi-Rosset, ‡Gustavo N. Simao, ∗ Lauro Wichert-Ana, ∗ Tonicarlo R. Velasco, ∗ Americo C. Sakamoto, ∗ Joao P. Leite, and ‡Antonio C. Santos Departments of ∗ Neurology–FMRP, †Physics–FFCLRP, and ‡Internal Medicine–FMRP, University of S˜ao Paulo, Ribeirao Preto, Brazil
Summary: Purpose: To analyze the patterns of brain activation in polymicrogyric cortex in epilepsy patients by blood oxygenation level–dependent (BOLD) functional MRI (f MRI), during language and motor activation tasks. Methods: Five patients with extratemporal epilepsy associated with polymicrogyria were scanned in a 1.5-T Siemens scanner with BOLD f MRI sequences, by following language and motor paradigms. Functional images were processed by using Brain Voyager software.
Results: Activation of polymicrogyric cortex in the brain area that corresponds to the motor strip was present in all patients. Language studies revealed activation of polymicrogyric cortex over Broca’s area in three cases. Conclusions: Functionality was shown in polymicrogyric areas. Therefore if surgical resection is indicated, a careful functional planning is necessary because of functionality of the polymicrogyric cortex. Key Words: Polymicrogyric cortex— Functionality—Functional MRI.
Polymicrogyria (PMG) is a disorder of cortical organization that may be due to genetic or prenatal causes. The finding is an irregular cortical surface with the presence of abnormally small gyri, detected by magnetic resonance imaging (MRI) (1). Clinical features include delayed milestones, spastic paresis, mental retardation, and seizures. Surgical series of malformations of cortical development (MCDs) have been reported with ≤50% of seizure freedom. However, polymicrogyrias have a worse postsurgical prognosis because of suboptimal resection around eloquent areas (2). Increasing evidence exists that neurons in polymicrogyric areas are functional (3); therefore functional mapping of such areas is critical in candidates for epilepsy surgery. We tried to explore the patterns of activation within polymicrogyric cortex of a series of five epilepsy patients submitted to presurgical evaluation with blood oxygenation level–dependent (BOLD) functional magnetic resonance imaging (f MRI).
confirm PMG. Informed consent was obtained from all patients, and our ethics committee approved the study. Patients were scanned in a 1.5-T scanner (Magneton Vision, Siemens, Erlangen, Germany). The f MRI was acquired in EPI-BOLD. A T1 -weighted anatomic volume also was acquired by using a 3D fast spoiled gradient echo sequence. We designed a block paradigm with six blocks of rest, interleaved with five blocks of activity. Sixty-eight scans were acquired in 4.5 min. For activation in Broca’s area, paradigms of word and category naming were performed. Subjects were cued to think silently of as many words as possible, starting with a specified letter. The subject continued for 27 s, until cued to stop. For category naming, the observer presented categories, and subjects had to think of elements of that specific group, until cued to stop. Unilateral finger tapping, of either the right or the left hand, was performed separately, with the same block paradigm, rest against task, in a regular-paced rate, around 3 cycles per second. To ensure task compliance, patients were trained before scanning, and a “dry run” was performed. All patients generated at least three words for each category and letter in the language dry run. Observers checked task compliance. Data were analyzed with Brain Voyager 4.96 (Brain Innovation, Maastricht, The Netherlands). f MRI data were inspected for motion and were preprocessed by using motion correction and spatial and temporal smoothing. Voxels were examined with a general linear model (GLM), and
METHODS MRI studies of five adult patients (three women) with extratemporal epilepsy were retrospectively evaluated to Accepted October 16, 2005. Address correspondence and reprint requests to Dr. A.C. Santos at Department of Internal Medicine, Radiology Center, Ribeir˜ao Preto School of Medicine, University of S˜ao Paulo, 14051-140 Ribeirao Preto, SP, Brazil. E-mail:
[email protected]
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4 6 R R 4/36/F 5/33/M
80 92
11 L 3/24/M
85
7 64 R 2/26/F
R, right; L, left; IQ, estimated intelligence quotient; MRI, magnetic resonance imaging; f MRI, functional MRI; BOLD, blood oxygenation level–dependent; BFPP, bilateral frontoparietal perisylvian polymicrogyria; PMG, polymicrogyria.
Activation of PMG on left inferior frontal area Activation of PMG on left inferior frontal area Activation of normal motor areas Bilateral activation of PMG and motor areas
(Movement artifact) Bilateral activation of PMG and motor areas
(Movement artifact) Bilateral activation of PMG and motor areas
Bilateral activation of PMG and motor areas
BFPP (asymmetric bilateral perisylvian polymicrogyria with motor and language areas involved) BFPP (asymmetric bilateral perisylvian polymicrogyria with motor and language areas involved) Frontoparietal with bilateral transmantel extension, arising the lateral ventricle at the left side Left temporoparietooccipital polymicrogyria BFPP (asymmetric bilateral perisylvian polymicrogyria with motor and language areas involved) 1 52 R
In a series of five patients with PMG, we found evidence of BOLD activation of polymicrogyric cortex in brain areas related with motor and language centers. As the link between BOLD f MRI signal and neuronal activity has been demonstrated, the activation patterns here described likely reflect neuronal activity. In agreement with our findings, evidence exists that polymicrogyric neurons may be functional, with alternative patterns of organization. These evidences come from clinical observations such as reflex epilepsies with seizures arising in polymicrogyric cortex, as well as from case reports of activation of medial dorsal complex cortex by f MRI or positron emission tomography (PET) studies (3,5–9). The statistical threshold was set to a high level to ensure high specificity. This may have decreased sensitivity, but it also avoided spurious activations due to artifacts or statistical errors. No regions of interest were selected a priori. Both phonetic and semantic tasks activated Broca’s area, probably because of more robust and specific activation. Function in PMG areas is not surprising, as patients with focal PMG are quite functional, and even patients with very extensive PMG involving eloquent areas may be able to perform language and motor tasks. The intrinsic functionality of PMG cortex must be considered in surgical planning and counseling for epilepsy patients with lesions in proximity to presumed eloquent areas.
1/23/F
DISCUSSION
MRI
Four patients were right-handed (three women), and one male patient was left-handed. None of them had a cognitive impairment severe enough to prevent task compliance. The results of the MRI can be seen in Table 1. All patients with perisylvian polymicrogyria and the patient with extensive frontoparietal polymicrogyria exhibited activation of the polymicrogyric cortex on motor tasks. The patterns of motor activity lay on portions of the posterior frontal lobe, within an area consistent with the precentral gyrus (Fig. 1). Patient 3 had no polymicrogyria over the motor strip but had bilateral activation to unilateral finger tapping, both left and right. Language studies showed statistically significant activation (p < 0.001) on GLM of the left inferior frontal regions, consistent with language centers in three cases (patients 1, 4, and 5) (see Fig. 2). In two cases (patients 2 and 3), movement artifacts prevented analysis of areas activated by language tasks.
TABLE 1. Demographic, neuropsychological, and imaging data of all patients
RESULTS
Motor task f MRI
Language task f MRI
regions with significant clusters (n > 6; p < 0.001) were selected. Neuropsychological examination was performed. Intellectual functioning of patients was assessed with the Revised Wechsler Adult Intelligence Scale (4).
Activation of PMG on left inferior frontal area
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Patient/ Years of Age/Sex Handedness IQ education
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fMRI ACTIVATION IN POLYMICROGYRIC CORTEX
591
FIG. 1. Top: Results of a patient with bilateral asymmetric polymicrogyria, showing a subtle right white-matter reduction, also in parietooccipital areas. Bottom: Statistical maps show activation of polymycrogyric cortex in response to a left finger-tapping paradigm.
Acknowledgment: This work was supported by FAPESP (The CINAPCE Project 05/56447-7), FAEPA, and CAPES. 3.
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FIG. 2. Top: T1 -weighted images from a patient with focal frontal polymicrogyric cortex. Bottom: Functional activation language center in response to a word-generation paradigm.
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