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.     

Determining language laterality by fMRI and dichotic listening

For imaging studies on hemispheric specialization of the human brain, data about known functional asymmetries other than handedness would be valuable for a reliable interpretation of lateralized activation in individuals or groups of subjects. As certain aspects of language processing are observed to be a function of primarily the left, it can be used as a reference for other asymmetric processes such as sensory or cognitive skills. For analyzing language laterality, there are a variety of methods, but these differ in application or accuracy. In this study, we tested the reliability of two widely used methods - dichotic listening and fMRI - to determine language dominance in 30 individual subjects. The German adaptation of a dichotic listening test (H?ttig, H., Beier, M., 2000. FRWT: a dichotic listening test for clinical and scientific contexts, Zeitschr f Neuropsychologie 11. 233-245.) classified 54% of the 26 right-handed subjects as left hemispheric dominant. The results of the fMRI paradigm (Fernández, G., de Greiff, A., von Oertzen, J., et al., 2001. Language mapping in less than 15 min: real-time functional MRI during routine clinical investigation. Neuroimage 14, 585-594.) tested on the same subjects, however, classified 92% of the right-handed subjects as left dominant. The main reason for this discrepancy was that the ear dominance score of many subjects in the dichotic listening test was too low to determine a reliable ear advantage. As a consequence, this specific dichotic listening test cannot be used to determine language laterality in individual subjects. On the other hand, the fMRI results are consistent with numerous studies showing left dominant language processing in more than 90% of right-handers. In some subjects, however, language laterality critically depends on the areas used to determine the laterality index.     

Hemispheric language dominance testing by means of fMRI.

Presurgical evaluation of patients with intractable epilepsy routinely includes hemispheric language dominance (HLD) testing. Commonly, HLD is assessed by the intracarotid amobarbital (Wada) test.¹ The advent of functional magnetic resonance imaging (fMRI) has generated considerable interest in this technique as an alternative to HLD testing.^2–6 Functional MRI mapping of the brain relies on the detection of focal changes in the concentrations of deoxyhemoglobin.⁷     

Unsuspected atypical hemispheric dominance for language as determined by fMRI

PURPOSE: We sought to illustrate the value of functional magnetic resonance imaging (fMRI) in the presurgical assessment of hemispheric dominance for language by means of an illustrative case report. METHODS: fMRI with two language paradigms was performed in a right-handed patient without familial sinistrality suffering from a left frontal focal epilepsy. RESULTS: Both fMRI paradigms revealed unequivocally lateralized right hemispheric activation. Atypical language representation was confirmed by Wada test. The further presurgical workup could be restricted to subdural strip recordings instead of the initially intended grid implantation. After resective surgery, no language deficits were apparent. CONCLUSIONS: Hemispheric dominance for language should be assessed by fMRI in all patients before surgery in areas potentially relevant for language in either cerebral hemisphere. fMRI may influence the further diagnostic workup and should be performed before other invasive diagnostic procedures.     

Seizure activity in vitro: a dual focus model

Recently, we have reported that the exposure of hippocampal slices in vitro to artificial cerebrospinal fluid (ACSF) containing no added magnesium results in ictal-like (ictaform) activity in area CA3 of the hippocampal formation. Other reports describe such activity in slices of entorhinal cortex (EC) under similar conditions. Because of the close interrelationship between the entorhinal area and the hippocampal formation, we have begun to study, in vitro, brain slices which contain both the entorhinal cortex and the hippocampal formation. In these slices, we have found that, in the magnesium-free (0-Mg2+) model, there is good electrical communication between area CA3 and the EC. Simultaneous recordings of the activity in the EC and CA3 showed that, when the circuitry linking the two areas was intact, the EC tended to initiate the ictaform activity and lead CA3. However, late in the event, CA3 could lead EC. Furthermore, interictal-like spontaneous bursting in CA3 led to a disorganized pattern of ictaform activity in EC. Finally, when the EC was separated from the hippocampal formation, both areas were capable of ictaform activity which was temporally unrelated. This model provides the opportunity to explore the relationship between two epileptogenic areas in vitro, and to compare and contrast the morphology of the ictaform activity present in both structures. As such, it may prove valuable in both pharmacological and physiological studies of seizure disorders.     

Electrophysiology meets fMRI: Neural correlates of the startle reflex assessed by simultaneous EMG–fMRI data acquisition

The startle reflex provides a unique tool for the investigation of sensorimotor gating and information processing. Simultaneous EMG–fMRI acquisition (i.e., online stimulation and recording in the MR environment) allows for the quantitative assessment of the neuronal correlates of the startle reflex and its modulations on a single trial level. This serves as the backbone for a startle response informed fMRI analysis, which is fed by data acquired in the same brain at the same time. We here present the first MR study using a single trial approach with simultaneous acquired EMG and fMRI data on the human startle response in 15 healthy young men. It investigates the neural correlates for isolated air puff startle pulses (PA), prepulse–pulse inhibition (PPI), and prepulse facilitation (PPF). We identified a common core network engaged by all three conditions (PA, PPI, and PPF), consisting of bilateral primary and secondary somatosensory cortices, right insula, right thalamus, right temporal pole, middle cingulate cortex, and cerebellum. The cerebellar vermis exhibits distinct activation patterns between the startle modifications. It is differentially activated with the highest amplitude for PPF, a lower activation for PA, and lowest for PPI. The orbital frontal cortex exhibits a differential activation pattern, not for the type of startle response but for the amplitude modification. For pulse alone it is close to zero; for PPI it is activated. This is in contrast to PPF where it shows deactivation. In addition, the thalamus, the cerebellum, and the anterior cingulate cortex add to the modulation of the startle reflex. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

Imaging language networks before and after anterior temporal lobe resection: results of a longitudinal fMRI study

Purpose: Anterior temporal lobe resection (ATLR) controls seizures in up to 70% of patients with intractable temporal lobe epilepsy (TLE) but, in the language dominant hemisphere, may impair language function, particularly naming. Functional reorganization can occur within the ipsilateral and contralateral hemispheres. We investigated reorganization of language in left‐hemisphere–dominant patients before and after ATLR; whether preoperative functional magnetic resonance imaging (fMRI) predicts postoperative naming decline; and efficiency of postoperative language networks. Methods: We studied 44 patients with TLE due to unilateral hippocampal sclerosis (24 left) on a 3T GE‐MRI scanner. All subjects performed language fMRI and neuropsychological testing preoperatively and again 4 months after left or right ATLR. Key Findings: Postoperatively, individuals with left TLE had greater bilateral middle/inferior frontal fMRI activation and stronger functional connectivity from the left inferior/middle frontal gyri to the contralateral frontal lobe than preoperatively, and this was not observed in individuals with right TLE. Preoperatively, in left and right TLE, better naming correlated with greater preoperative left hippocampal and left frontal activation for verbal fluency (VF). In left TLE, stronger preoperative left middle frontal activation for VF was predictive of greater decline in naming after ATLR. Postoperatively, in left TLE with clinically significant naming decline, greater right middle frontal VF activation correlated with better postoperative naming. In patients without postoperative naming decline, better naming correlated with greater activation in the remaining left posterior hippocampus. In right TLE, naming ability correlated with left hippocampal and left and right frontal VF activation postoperatively. Significance: In left TLE, early postoperative reorganization to the contralateral frontal lobe suggests multiple systems support language function. Postoperatively, ipsilateral recruitment involving the posterior hippocampal remnant is important for maintaining language, and reorganization to the contralateral hemisphere is less effective. Preoperative left middle frontal activation for VF was predictive of naming decline in left TLE after ATLR.     

Defining language networks from resting‐state fMRI for surgical planning—a feasibility study

Presurgical language mapping for patients with lesions close to language areas is critical to neurosurgical decision‐making for preservation of language function. As a clinical noninvasive imaging technique, functional MRI (fMRI) is used to identify language areas by measuring blood‐oxygen‐level dependent (BOLD) signal change while patients perform carefully timed language vs. control tasks. This task‐based fMRI critically depends on task performance, excluding many patients who have difficulty performing language tasks due to neurologic deficits. On the basis of recent discovery of resting‐state fMRI (rs‐fMRI), we propose a “task‐free” paradigm acquiring fMRI data when patients simply are at rest. This paradigm is less demanding for patients to perform and easier for technologists to administer. We investigated the feasibility of this approach in right‐handed healthy control subjects. First, group independent component analysis (ICA) was applied on the training group (14 subjects) to identify group level language components based on expert rating results. Then, four empirically and structurally defined language network templates were assessed for their ability to identify language components from individuals' ICA output of the testing group (18 subjects) based on spatial similarity analysis. Results suggest that it is feasible to extract language activations from rs‐fMRI at the individual subject level, and two empirically defined templates (that focuses on frontal language areas and that incorporates both frontal and temporal language areas) demonstrated the best performance. We propose a semi‐automated language component identification procedure and discuss the practical concerns and suggestions for this approach to be used in clinical fMRI language mapping. Hum Brain Mapp 35:1018–1030, 2014. © 2013 Wiley Periodicals, Inc.     

On understanding idiomatic language: The salience hypothesis assessed by ERPs

Giora's [Giora, R., 1997. Understanding figurative and literal language: the Graded Salience Hypothesis. Cogn. Linguist. 7 (1), 183-206; Giora, R., 2003. On Our Mind: Salience Context and Figurative Language. Oxford Univ. Press, New York] Graded Salience Hypothesis states that more salient meanings-coded meanings foremost on our mind due to conventionality, frequency, familiarity, or prototypicality-are accessed faster than and reach sufficient levels of activation before less salient ones. This research addresses predictions derived from this model by examining the salience of familiar and predictable idioms, presented out of context. ERPs recorded from 30 subjects involved in reading and lexical decision tasks to (strongly/weakly) salient idioms and (figurative/literal) targets indicate that N400 amplitude was smaller for the last word of the strongly salient idioms than for the weakly salient idioms. Moreover, N400 amplitude of probes related to the salient meaning of strongly salient idioms was smaller than those of the 3 other conditions. In addition, response times to salient interpretations (the idiomatic meanings of highly salient idioms and the literal interpretations of less salient idioms) were shorter compared to the other conditions. These findings support Giora's Graded Salience Hypothesis. They show that salient meanings are accessed automatically, regardless of figurativity.     

Line bisection judgments implicate right parietal cortex and cerebellum as assessed by fMRI

OBJECTIVE: To use functional MRI (fMRI) to determine which brain regions are implicated when normal volunteers judge whether pretransected horizontal lines are correctly bisected (the Landmark test). BACKGROUND: Manual line bisection and a variant thereof involving perceptual judgments of pretransected lines (the Landmark test) are widely used to assess unilateral visuospatial neglect in patients with neurologic disease. Although unilateral (left) neglect most often results from lesions to right temporoparietal cortex, the normal functional anatomy of the Landmark test has not been convincingly demonstrated. METHODS: fMRI was carried out in 12 healthy right-handed male volunteers who judged whether horizontal lines were correctly prebisected. In the control task, subjects detected whether the horizontal lines contained a transection mark irrespective of the position of that mark. Response was by two-choice key press: on half the trials, subjects used the right, and on half, the left hand. Statistical analysis of evoked blood oxygenation level-dependent responses, measured with echoplanar imaging, employed statistical parametric mapping. RESULTS: Performing the Landmark task showed neural activity (p < 0.05, corrected) in the right superior posterior and right inferior parietal lobe, early visual processing areas bilaterally, the cerebellar vermis, and the left cerebellar hemisphere. Only the latter area showed a significant interaction with hand used. CONCLUSIONS: The right hemispheric dominance observed in inferior parietal cortex is consistent with the results of lesion studies. Right superior parietal cortex, vermis, and left cerebellar hemisphere have not been implicated in neglect, but all appear to play a cognitive role in the Landmark task.     

Relationship between motor and language activation using fMRI

The authors examined laterality ratios (i.e., [L-R]/[L+R]) from functional MRI (fMRI) scans obtained in 12 healthy volunteers during unimanual left- and right-hand finger movements and during a verb generation language task. The language and right-hand motor asymmetry ratios were correlated (rho = 0.71, p = 0.005) as were the left- and right-hand ratios (rho = -0.68, p = 0.008). Subjects with greater relative left hemisphere lateralization of language exhibit greater relative unilateral hemisphere activation during right-hand movements.     

Impaired perceptual networks in temporal lobe epilepsy revealed by resting fMRI

Viewed as a neural network disorder, mesial temporal lobe epilepsy (mTLE) may cause widespread deficits in human brain functions. Impairments in cognitive functions such as memory and language have been well addressed, but perceptual deficits have only been considered in terms of behavioral data. Little imaging research on perceptual deficits in mTLE has been reported. The present study is expected to reveal impairments in the perceptual networks in patients with mTLE using fMRI. The fMRI-based independent component analysis (ICA) was applied to 33 patients with mTLE and 33 matched healthy controls. In light of the resting-state networks (RSNs) corresponding to the basal functions of visual, auditory, and sensorimotor systems, the ICA data of functional connectivity within these RSNs were compared between the patients and controls. Compared with the controls, the mTLE patients presented decreased functional connectivity within the regions of the auditory and sensorimotor networks, as well increased functional connectivity in the primary visual cortex and decreased functional connectivity in the bilateral MT+ areas of the visual network. Our neuroimaging results are in agreement with the previous findings that specific perceptual functions are impaired in mTLE. Furthermore, our findings in the visual network support the belief that the primary visual function is not impaired and that there may be deficits in the high-order visual function in mTLE. Our fMRI study may contribute to the understanding of neuropathophysiological mechanisms underlying perceptual impairments in mTLE.     

Endogenous brain oscillations and related networks detected by surface EEG-combined fMRI

It is difficult to study the brain "at rest" with an approach generally pursued in science when external manipulation (independent variable) is used to obtain informative measurements (dependent variable) about the object of interest. External manipulation in its classic sense may suspend the resting state, and hence the object of interest will evade. Naturally, unless in a final and irreversible state, biological rest will always be an endogenously dynamic process. Combining two modalities, electroencephalography (EEG) and functional magnetic resonance imaging (fMRI), to simultaneously measure the brain's activity from two angles, one can be chosen to be interpreted as the independent variable and the other as the dependent variable, and without external manipulation the brain's spontaneous dynamics can be studied. The EEG, for example, observes endogenous modulations of vigilance and detects spontaneous events such as sleep spindles or epileptic discharges and can be used as the independent variable, i.e., to form a regressor to interrogate the fMRI data (dependent variable). The opposite is possible as well, and data fusion attempts try using all data both as dependent and independent variables at the same time. This review limits itself to an exemplary discussion of simultaneous EEG/fMRI studies in humans, and among a variety of proposed resting state networks only discusses a few, especially those for which non-resting state literature has proposed a functional meaning: the "default mode" network and an attentional network. It will be shown that one EEG feature can correlate with different fMRI activation maps and that a single resting state network may be associated with a variety of EEG patterns giving insight into the function of different resting states and the relationship between the two modalities in themselves.     

Seizure generation: The role of nodes and networks

The longstanding dichotomy between the concepts of "focal" and "primary generalized" epilepsy has become increasingly blurred, raising fundamental questions about the nature of ictal onset in localized brain regions versus large-scale brain networks. We hypothesize that whether an EEG discharge appears focal or generalized is driven by the pattern of connections in brain networks, irrespective of the presence of focal brain abnormality. Using a computational model of a simple "brain" consisting of four regions and the connections between them, we explored the effects of altering connectivity structure versus the effects of introducing an "abnormal" brain region, and the interactions between these factors. Computer simulations demonstrated that electroencephalography (EEG) discharges representing either generalized or focal seizures arose purely as a consequence of subtle changes in network structure, without the requirement for any localized pathologic brain region. Furthermore we found that introducing a pathologic region gave rise to focal, secondary generalized, or primary generalized seizures depending on the network structure. Counterintuitively, we found that decreasing connectivity between regions of the brain increased the frequency of seizure-like activity. Our findings may enlighten current controversies surrounding the concepts of focal and generalized epilepsy, and help to explain recent observations in genetic animal models and human epilepsies, where loss of white matter pathways was associated with the occurrence of seizures.