Language lateralization in left-handed and ambidextrous people: fMRI data

BACKGROUND: It is generally accepted that most people have left-hemispheric language dominance, though the actual incidence of atypical language distribution in non-right-handed subjects has not been extensively studied. The authors examined language distribution in these subjects and evaluated the relationships between personal handedness, family history of sinistrality, and a language laterality index (LI) measured with fMRI. METHODS: The authors used whole-brain fMRI to examine 50 healthy, non-right-handed subjects (Edinburgh Handedness Inventory quotient between -100 and 52) while they performed language activation and nonlinguistic control tasks. Counts of active voxels (p < 0.001) were computed in 22 regions of interest (ROI) covering both hemispheres and the cerebellum. LI were calculated for each ROI and each entire hemisphere using the formula [L - R]/[L + R]. RESULTS: Activation was predominantly right hemispheric in 8% (4/50), symmetric in 14% (7/50), and predominantly left hemispheric in 78% (39/50) of the subjects. Lateralization patterns were similar for all hemispheric ROI. Associations were observed between personal handedness and LI (r = 0.28, p = 0.046), family history of sinistrality and LI (p = 0.031), and age and LI (r = -0.49, p < 0.001). CONCLUSIONS: The incidence of atypical language lateralization in normal left-handed and ambidextrous subjects is higher than in normal right-handed subjects (22% vs 4-6%). These whole-brain results confirm previous findings in a left-handed cohort studied with fMRI of the lateral frontal lobe. Associations observed between personal handedness and LI and family history of handedness and LI may indicate a common genetic factor underlying the inheritance of handedness and language lateralization.     

Pathology type does not predict language lateralization in children with medically intractable epilepsy

Purpose: We examined potential differences in the effects of pathology type on language lateralization in pediatric epilepsy. Methods: We examined findings from intracarotid sodium amobarbital procedure (IAP/Wada) in a large consecutive sample of children with refractory epilepsy. Subjects were assigned to one of three pathology groups: developmental (n = 28), acquired (n = 26), and tumor (n = 20); groups were compared for language lateralization. Results: Rates of atypical language lateralization did not differ across groups. Greater than half of the subjects with left hemisphere insults and seizure onset before 6 years of age had atypical language lateralization, independent of pathology type. Discussion: Atypical language lateralization may occur in the context of developmental, acquired, and/or tumor pathology.     

Arcuate fasciculus asymmetry has a hand in language function but not handedness

The importance of relationships between handedness, language lateralization and localization, and white matter tracts for language performance is unclear. The goal of the study was to investigate these relationships by examining arcuate fasciculus (AF) structural asymmetry (DTI) and functional asymmetry (fMRI) in language circuits, handedness, and linguistic performance. A large sample of right‐handed (n = 158) and atypical‐handed (n = 82) healthy adults underwent DTI at 3 T to assess number of streamlines and fractional anisotropy (FA) of the AF, and language fMRI. Language functions were assessed using standard tests of vocabulary, naming, verbal fluency, and complex ideation. Laterality indices (LIs) illustrated degree of asymmetry and lateralization patterns for the AF (streamlines and FA) and verb generation fMRI. Both handedness groups showed leftward lateralization bias for streamline and fMRI LIs and symmetry for FA LI. The proportion of subjects with left, right, or symmetric lateralization were similar between groups if based on AF LIs, but differed if based on fMRI LIs (p = 0.0016). Degree of right‐handedness was not associated with AF lateralization, but was associated with fMRI language lateralization (p = 0.0014). FA LI was not associated with performance on language assessments, but streamline LI was associated with better vocabulary and complex ideation performance in atypical‐handed subjects (p = 0.022 and p = 0.0098, respectively), and better semantic fluency in right‐handed subjects (p = 0.047); however, these did not survive multiple comparisons correction. We provide evidence that AF asymmetry is independent of hand preference, and while degree of right‐handedness is associated with hemispheric language lateralization, the majority of atypical‐handed individuals are left‐lateralized for language. Hum Brain Mapp 37:3297–3309, 2016. © 2016 Wiley Periodicals, Inc .     

Is Language Lateralization in Temporal Lobe Epilepsy Patients Related to the Nature of the Epileptogenic Lesion?

PURPOSE: Early acquired lesions are considered to be a risk factor for atypical language lateralization in epilepsy, whereas developmental lesions are not. Hippocampal sclerosis (HS) can be understood as an early, acquired lesion, whereas developmental tumors (DT) are thought to originate in utero. We assessed whether language lateralization differs between these groups of temporal lobe epilepsy patients. METHODS: We used 3-Tesla functional MRI (fMRI) to assess 41 patients (16 DT, 25 HS) and 50 controls, performing a noun-verb-generation task. fMRI data were processed by using SPM2. A laterality index (LI) was calculated based on the number of activated voxels in left- and right-sided frontal lobe language areas. Atypical lateralization was considered if the index was < or = 0.2. RESULTS: Patients had a lower LI (0.42 +/- 0.5) than controls (0.6 +/- 0.3; p < or = 0.05), but the LI was not different between DT (0.44 +/- 0.5) and HS patients (0.43 +/- 0.4; p = 0.9). The frequency of atypical lateralization was increased in patients (27%) compared with controls (8%) but was similar in both patient groups (DT, 31%; HS, 24%). HS patients had an earlier onset and longer duration of epilepsy and a higher frequency of significant antecedent events (p < or = 0.05). CONCLUSIONS: Patients with TLE demonstrate a deviation toward atypical language lateralization. However, language lateralization was not different between patients with presumably acquired lesions compared with patients with developmental pathology. This suggests that the nature of the temporal lobe lesion does not influence overall language lateralization.     

Language lateralization correlates with verbal memory performance in children with focal epilepsy

Purpose: Assessment of language dominance with functional magnetic resonance imaging (fMRI) and neuropsychological evaluation is often used prior to epilepsy surgery. This study explores whether language lateralization and cognitive performance are systematically related in young patients with focal epilepsy. Methods: Language fMRI and neuropsychological data (language, visuospatial functions, and memory) of 40 patients (7–18 years of age) with unilateral, refractory focal epilepsy in temporal and/or frontal areas of the left (n = 23) or right hemisphere (n = 17) were analyzed. fMRI data of 18 healthy controls (7–18 years) served as a normative sample. A laterality index was computed to determine the lateralization of activation in three regions of interest (frontal, parietal, and temporal). Results: Atypical language lateralization was demonstrated in 12 (30%) of 40 patients. A correlation between language lateralization and verbal memory performance occurred in patients with left‐sided epilepsy over all three regions of interest, with bilateral or right‐sided language lateralization being correlated with better verbal memory performance (Word Pairs Recall: frontal r = ?0.4, p = 0.016; parietal r = ?0.4, p = 0.043; temporal r = ?0.4, p = 0.041). Verbal memory performance made the largest contribution to language lateralization, whereas handedness and side of seizures did not contribute to the variance in language lateralization. Discussion: This finding reflects the association between neocortical language and hippocampal memory regions in patients with left‐sided epilepsy. Atypical language lateralization is advantageous for verbal memory performance, presumably a result of transfer of verbal memory function. In children with focal epilepsy, verbal memory performance provides a better idea of language lateralization than handedness and side of epilepsy and lesion.     

Comprehensive presurgical functional MRI language evaluation in adult patients with epilepsy

Functional magnetic resonance imaging (fMRI) has the potential to replace the intracarotid amobarbital procedure (IAP) in presurgical evaluation of patients with epilepsy. In this study, we compared fMRI verb generation (VG) and semantic decision/tone decision (SDTD) tasks and the IAP in their ability to localize language functions in patients with epilepsy undergoing presurgical evaluation. We enrolled 50 healthy controls to establish normal language activation patterns for VG and SDTD tasks at 3 or 4 T, and to design language regions of interest (ROIs) that were later applied to 38 patients with epilepsy (28 of 38 also underwent the IAP). We calculated laterality indices (LIs) for each task for each subject based on the ROIs, and we used general linear modeling to analyze the fMRI data. All healthy and epileptic subjects activated language areas with both fMRI tasks. We found significant correlations in language lateralization between the fMRI tasks (r=0.495, P<0.001) and between VG and IAP (r=0.652, P<0.001) and SDTD and IAP (r=0.735, P<0.001). The differences in LIs between SDTD and VG tasks were small and not affected by age, gender, epilepsy status, handedness, or performance. SDTD and VG tasks combined explained approximately 58.4% in the variability of the IAP/language. In the general linear modeling, only the SDTD task significantly contributed to the determination of language lateralization in patients with epilepsy undergoing presurgical evaluation. Results indicate a moderate convergent validity between both fMRI language tasks and between IAP and fMRI tasks. The results of this study indicate that either of these fMRI tasks can be used for language lateralization in patients with epilepsy undergoing presurgical evaluation, but that the SDTD task is likely to provide more information regarding language lateralization than the VG task.     

Correlation between language organization and diffusion tensor abnormalities in refractory partial epilepsy

PURPOSE: Atypical language organization is more frequently found in patients with refractory partial epilepsy than in healthy controls; however, the reasons for this are not well known. Here we assess the relation between language laterality index (LI) and white-matter tract changes. METHODS: Nine patients with refractory partial epilepsy were assessed with a 3-T GE scanner. Functional magnetic resonance imaging (fMRI) of language and diffusion tensor imaging (DTI) were acquired. For the fMRI, a noun-verb generation task was performed, all images were motion corrected, and activated pixels in classic language areas were counted. The DTI images were acquired in six standard directions with an initial non-diffusion-weighted scan. The "average anisotropy" was determined in a region of interest in the frontal lobe, temporal lobe, and parietal lobe white matter. An asymmetry index (AI) was calculated for language and DTI. Atypical language lateralization was diagnosed if the lateralization index (LI)-language was smaller than 0.4. RESULTS: Two of the nine patients had atypical language localization (LI-language, -0.6, and 0.3); both had left temporal DTI asymmetry (LI-DTI, -0.3 and -0.2). The remaining seven patients had typical language localization, and no marked DTI abnormalities. Asymmetry in temporal lobe DTI correlated with LI-language (r= 0.8; p = 0.006). CONCLUSIONS: Atypical language lateralization in patients with partial epilepsy may be associated with white-matter tract abnormalities.     

Topiramate and its effect on fMRI of language in patients with right or left temporal lobe epilepsy

Topiramate (TPM) is well recognized for its negative effects on cognition, language performance and lateralization results on the intracarotid amobarbital procedure (IAP). But, the effects of TPM on functional MRI (fMRI) of language and the fMRI signals are less clear. Functional MRI is increasingly used for presurgical evaluation of epilepsy patients in place of IAP for language lateralization. Thus, the goal of this study was to assess the effects of TPM on fMRI signals. In this study, we included 8 patients with right temporal lobe epilepsy (RTLE) and 8 with left temporal lobe epilepsy (LTLE) taking TPM (+TPM). Matched to them for age, handedness and side of seizure onset were 8 patients with RTLE and 8 with LTLE not taking TPM (-TPM). Matched for age and handedness to the patients with TLE were 32 healthy controls. The fMRI paradigm involved semantic decision/tone decision task (in-scanner behavioral data were collected). All epilepsy patients received a standard neuropsychological language battery. One sample t-tests were performed within each group to assess task-specific activations. Functional MRI data random-effects analysis was performed to determine significant group activation differences and to assess the effect of TPM dose on task activation. Direct group comparisons of fMRI, language and demographic data between patients with R/L TLE +TPM vs. -TPM and the analysis of the effects of TPM on blood oxygenation level-dependent (BOLD) signal were performed. Groups were matched for age, handedness and, within the R/L TLE groups, for the age of epilepsy onset/duration and the number of AEDs/TPM dose. The in-scanner language performance of patients was worse when compared to healthy controls - all p<0.044. While all groups showed fMRI activation typical for this task, regression analyses comparing L/R TLE +TPM vs. -TPM showed significant fMRI signal differences between groups (increases in left cingulate gyrus and decreases in left superior temporal gyrus in the patients with LTLE +TPM; increases in the right BA 10 and left visual cortex and decreases in the left BA 47 in +TPM RTLE). Further, TPM dose showed positive relationship with activation in the basal ganglia and negative associations with activation in anterior cingulate and posterior visual cortex. Thus, TPM appears to have a different effect on fMRI language distribution in patients with R/L TLE and a dose-dependent effect on fMRI signals. These findings may, in part, explain the negative effects of TPM on cognition and language performance and support the notion that TPM may affect the results of language fMRI lateralization/localization.     

Functional deficit in the medial prefrontal cortex during a language comprehension task in patients with schizophrenia

OBJECTIVE: We and others have observed that patients with schizophrenia commonly presented a reduced left recruitment in language semantic brain regions. However, most studies include patients with leftward and rightward lateralizations for language. We investigated whether a cohort comprised purely of patients with typical lateralization (leftward) presented a reduced left recruitment in semantic regions during a language comprehension task. The goal was to reduce the inter-subject variability and thus improve the resolution for studying functional abnormalities in the language network. METHODS: Twenty-three patients with schizophrenia (DSM-IV) were matched with healthy subjects in age, sex, level of education and handedness. All patients exhibited leftward lateralization for language. Functional MRI was performed as subjects listened to a story comprising characters and social interactions. Functional MRI signal variations were analyzed individually and compared among groups. RESULTS: Although no differences were observed in the recruitment of the semantic language network, patients with schizophrenia presented significantly lower signal variations compared to controls in the medial part of the left superior frontal gyrus (MF1) (x=-6, y=58, z=20; Z(score)=5.6; p<0.001 uncorrected). This region corresponded to the Theory of Mind (ToM) network. Only 5 of the 23 patients (21.7%) and 21 of the 23 (91.3%) control subjects demonstrated a positive signal variation in this area. CONCLUSIONS: A left functional deficit was observed in a core region of the ToM network in patients with schizophrenia and typical lateralizations for language. This functional defect could represent a neural basis for impaired social interaction and communication in patients with schizophrenia.     

Reduced language lateralization in first-episode medication-naive schizophrenia

Diminished functional lateralization in language-related areas is found in chronic schizophrenia. It is not clear at what stage of illness these abnormalities in lateralization arise, or whether they are affected by medication. In addition, it is hypothesized that reduced language lateralization is related to positive symptoms of schizophrenia, but studies addressing this issue have yielded contradictory results. In this study we used functional MRI to measure language lateralization in 35 first-episode medication-naive schizophrenia patients and 43 matched healthy controls. Subjects performed three language tasks: a paced verb generation task, an antonym generation task, and a semantic decision task. Lateralization Index (LI) was calculated, using a relative threshold technique, in seven Regions of Interest (ROIs), including the main language-related areas and their contralateral homologues. In addition, we investigated whether language lateralization was correlated with psychotic symptoms. Across all ROIs, LI was significantly reduced in patients (p<0.001) compared to controls. Post-hoc tests revealed that this reduction was most prominent in the inferior frontal gyrus (part of Broca's area) (p=0.003) and the superior temporal gyrus (part of Wernicke's area) (p<0.001). LI was not correlated with the positive subscale of the PANSS, nor with hallucinations or disorganization. This is the first study to report reduced LI at the onset of schizophrenia, before medical treatment is initiated.     

The effect of seizure focus on regional language processing areas

Purpose: To determine the effect of seizure focus location within the left hemisphere on the expression of regional language dominance. Methods: In this cross‐sectional study we investigated 90 patients (mean age 23.3 ± 12.9 years) with left hemisphere focal epilepsy (mean age onset 11.7 ± 8.3 years). Eighteen patients had a frontal lobe focus and 72 had a temporal lobe focus (43 mesial; 29 neocortical). Subjects performed an auditory word definition language paradigm using 3 Tesla blood oxygen level dependent (BOLD) EPI functional magnetic resonance imaging (fMRI). Data were analyzed in SPM2. Regional laterality indices (LIs) for inferior frontal gyrus (IFG), and Wernicke’s area (WA), were calculated using a bootstrap method. Categorical language dominance and mean LI were analyzed. Key Findings: Mean WA LI was lower for subjects with a mesial temporal focus compared with a frontal focus (p = 0.04). There was a greater proportion of atypical language in WA for subjects with a mesial temporal focus compared with a frontal focus (χ² = 4.37, p = 0.04). WA LI did not differ for subjects with a neocortical focus compared with a mesial focus or a frontal focus. Mean IFG LI and proportion of atypical language in IFG were similar across seizure focus groups. Age and age of onset were not correlated with mean laterality in WA or IFG. Epilepsy duration tended to be negatively correlated with WA LI (r = ?0.18, p = 0.10), but not IFG LI. Significance: Temporal lobe foci have wide‐ranging effects on the distributed language system. In contrast, the effects of a frontal lobe focus appear restricted to anterior rather than posterior language processing areas.     

Clinical functional MRI of the language domain in children with epilepsy

Functional MRI (fMRI) for the assessment of language functions is increasingly used in the diagnostic workup of patients with epilepsy. Termed "clinical fMRI," such an approach is also feasible in children who may display specific patterns of language reorganization. This study was aimed at assessing language reorganization in pediatric epilepsy patients, using fMRI. We studied 26 pediatric epilepsy patients (median age, 13.05 years; range, 5.6-18.7 years) and 23 healthy control children (median age, 9.37 years; range, 6.2-15.4 years), using two child-friendly fMRI tasks and adapted data-processing streams. Overall, 81 functional series could be analyzed. Reorganization seemed to occur primarily in homotopic regions in the contralateral hemisphere, but lateralization in the frontal as well as in the temporal lobes was significantly different between patients and controls. The likelihood to find atypical language organization was significantly higher in patients. Additionally, we found significantly stronger activation in the healthy controls in a primarily passive task, suggesting a systematic confounding influence of antiepileptic medication. The presence of a focal cortical dysplasia was significantly associated with atypical language lateralization. We conclude that important confounds need to be considered and that the pattern of language reorganization may be distinct from the patterns seen in later-onset epilepsy.     

Medial temporal fMRI activation reflects memory lateralization and memory performance in patients with epilepsy

Memory difficulties are a frequent cognitive complaint of patients with chronic epilepsy. Previous studies have suggested that the presence of a seizure focus causes reorganization of brain mechanisms underlying memory function. Here we examine whether seizure onset in the left hemisphere and onset in the right hemisphere have different effects on memory lateralization and whether longer duration of epilepsy is associated with increased lateralization of memory functions to the unaffected hemisphere. We hypothesized that hemisphere of onset and duration of epilepsy would influence plasticity of memory mechanisms, similar to the plasticity observed for language mechanisms. Healthy controls (HC, N = 10) and patients with epilepsy (N = 23, 11 with a left- and 12 with a right-hemisphere focus) performed a scene-encoding fMRI task at 4 T. Active voxels (relative to scrambled image viewing) were identified for each participant. Memory laterality indices (LIs) were calculated in three regions of interest (ROIs) designed on the basis of HC group data: a functional ROI, an anatomical-hippocampal ROI, and an anatomical-medial temporal ROI encompassing hippocampus and parahippocampal gyrus. In healthy controls, LIs were suggestive of slight left lateralization of encoding memory for pictures. Patients with right hemisphere epilepsy showed a nonsignificant increase in degree of left lateralization. In contrast, patients with left hemispheric epilepsy showed right-lateralized activation, differing significantly from controls and from patients with right hemispheric epilepsy. Neuropsychological measures of memory (WMS-III Story Recall) across epilepsy patients predicted LIs in the anatomical ROIs: higher scores were associated with more left-lateralized medial temporal fMRI activation. Neither age of onset nor duration of epilepsy was significantly related to LI. These results indicate that focal epilepsy may influence the functional neuroanatomy of memory function.     

Functional MRI evidence for language plasticity in adult epileptic patients: Preliminary results

The present fMRI study explores the cerebral reorganisation of language in patients with temporal lobe epilepsy, according to the age of seizures onset (early or late) and the hippocampal sclerosis (associated or not). Seven right-handed control volunteers and seven preoperative adult epileptic patients performed a rhyme decision (language condition) and a visual detection (control condition) tasks in visually presented words and unreadable characters, respectively. All patients were left hemisphere dominant for language. Appropriate statistical analyses provided the following preliminary results: (1) patients compared with healthy subjects showed lower degree of hemispheric lateralization with supplementary involvement of the right hemisphere; (2) the degree of hemispheric specialization depends on the considered region; (3) patients with early seizures show signs of temporal and parietal reorganization more frequently than patients with late onset of seizures; (4) patients with early seizures show a tendency for intra-hemispheric frontal reorganisation; (5) associated hippocampal sclerosis facilitates the inter-hemispheric shift of temporal activation. Although our patients were left hemisphere predominant for language, the statistical analyses indicated that the degree of lateralization was significantly lower than in healthy subjects. This result has been considered as the indication of atypical lateralization of language.     

Strengthening of laterality of verbal and visuospatial functions during childhood and adolescence

Cognitive functions in the child's brain develop in the context of complex adaptive processes, determined by genetic and environmental factors. Little is known about the cerebral representation of cognitive functions during development. In particular, knowledge about the development of right hemispheric (RH) functions is scarce. Considering the dynamics of brain development, localization and lateralization of cognitive functions must be expected to change with age. Twenty healthy subjects (8.6-20.5 years) were examined with fMRI and neuropsychological tests. All participants completed two fMRI tasks known to activate left hemispheric (LH) regions (language tasks) and two tasks known to involve predominantly RH areas (visual search tasks). A laterality index (LI) was computed to determine the asymmetry of activation. Group analysis revealed unilateral activation of the LH language circuitry during language tasks while visual search tasks induced a more widespread RH activation pattern in frontal, superior temporal, and occipital areas. Laterality of language increased between the ages of 8-20 in frontal (r = 0.392, P = 0.049) and temporal (r = 0.387, P = 0.051) areas. The asymmetry of visual search functions increased in frontal (r = -0.525, P = 0.009) and parietal (r = -0.439, P = 0.027) regions. A positive correlation was found between Verbal-IQ and the LI during a language task (r = 0.585, P = 0.028), while visuospatial skills correlated with LIs of visual search (r = -0.621, P = 0.018). To summarize, cognitive development is accompanied by changes in the functional representation of neuronal circuitries, with a strengthening of lateralization not only for LH but also for RH functions. Our data show that age and performance, independently, account for the increases of laterality with age.     

Possible remote functional reorganization in left temporal lobe epilepsy

Objective –  To provide functional magnetic resonance imaging-based insight into the impact of left temporal lobe epilepsy (TLE) on language-related functional re-organization.
Materials and methods –  Ten right-handed patients with left TLE were compared with 10 matched healthy controls. Regional brain activation during the language task was measured in the inferior frontal gyrus (IFG) and in the superior temporal gyrus (STG), and the regional inter-hemispheric lateralization index (LI) was calculated.
Results –  Left language lateralization was documented in all the patients and controls. Reduced lateralization in the IFG was due to decreased activity in the left frontal region rather than to increased activity in the right frontal region. The LI values in the STG correlated with the LI values in the IFG in the controls but not in the patients.
Conclusions –  The left IFG was most probably involved in the epileptogenesis and concomitant language-related cortical plasticity in patients with left TLE.     

Determination of cortical language dominance using functional transcranial Doppler sonography in left-handers.

OBJECTIVE: Verbal analytical functions are primarily related to the left hemisphere in right-handers, but there is yet no agreement about cortical language dominance in left-handers. Also, there are some contradictory reports about sex differences in cortical language lateralization. The aim of this study is to investigate cortical language dominance in left-handers and to explore gender influence on cortical language representation. METHODS: We performed functional transcranial Doppler sonography (previous validated for determination of cerebral language lateralization) during a word generation task, measuring changes in mean cerebral blood flow velocity (BFVmean) in both middle cerebral arteries (MCA) in 150 healthy subjects (75 left-handers and 75 right-handers). In left-handers we observed significant increase BFVmean in right MCA in 58 (77.3%) subjects. Bilateral increase was observed in 11 (14.7%) subjects and increase in left MCA in 6 (8%) subjects. In right-handed group 93.3% subjects showed left cortical dominance, while 6.7% showed bilateral language representation. RESULTS: Current results showed significant (P<0.0001) right hemispheric language dominance in healthy left-handed subjects. CONCLUSIONS: Our results showed significant difference in hemispheric dominance for verbal function between righthanders and lefthanders. Also there is statistically insignificant female gender tendency for bilateral hemispheric language representation in both handedness.     

Multidrug resistance in patients undergoing resective epilepsy surgery is not associated with C3435T polymorphism in the ABCB1 (MDR1) gene

PURPOSE: The C3435T polymorphism in the gene coding for P-glycoprotein (ABCB1) has been correlated with drug resistance in patients with epilepsy. However, replication studies have revealed conflicting results and the reason for this is not clear. We investigated the frequency of C3435T polymorphism in epileptic Turkish patients who underwent resective epilepsy surgery and compared our results with healthy controls. METHODS: DNA samples were obtained from 100 healthy controls and 89 consecutive adult patients who underwent resective brain surgery due to refractory seizures at our epilepsy center. Genotypes for the C3435T polymorphism were determined by PCR and restriction analysis. RESULTS: Comparison of drug-resistant patients and healthy controls revealed no significant difference in allele frequency (C vs. T; chi(2)=0.015, p=0.90) and genotype frequency (chi(2)=2.05, p=0.36). The findings in the pure hippocampal sclerosis (HS) group (n=73) were not significantly different from control subjects, either (allele frequency: chi(2)=0.29, p=0.59; genotype frequency: chi(2)=2.14, p=0.34). CONCLUSIONS: Our findings failed to prove an association between C3435T polymorphism and drug resistance in a sample of Turkish patients with refractory epilepsy who underwent resective brain surgery.     

fMRI memory assessment in healthy subjects: a new approach to view lateralization data at an individual level

We present a comprehensive and clinically applicable fMRI test—including both a verbal and a visuospatial task—for assessment of hemispheric specific memory in the medial temporal lobe (MTL). fMRI data was collected from 15 healthy right-handed volunteers. Whole-brain activation was analyzed as well as activation in two regions of interest: the MTL and the anterior speech area. Laterality indices (LI) and LI-curves were calculated using the LI toolbox of Wilke and Lidzba, 2007. The fMRI paradigms successfully visualized memory-related activity in the MTL, the verbal memory measure also provided information of language lateralization. Eleven subjects showed left lateralized verbal encoding in the MTL, visuospatial memory activation was divided equally between left and right, and 14/15 subjects had left lateralized language. Lateralization data at the group level were consistent with previous studies, but a variety of activation effects were found at the individual level indicating differences in strategy during verbal and visuospatial processing. Further studies using the presented method are needed to determine its clinical usefulness.