The utility of magnetoencephalography in the presurgical evaluation of refractory insular epilepsy.

PURPOSE: To study the utility of magnetoencephalography (MEG) in patients with refractory insular epilepsy. Covered by highly functional temporal, frontal, and parietal opercula, insular-onset seizures can manifest a variety of ictal symptoms falsely leading to a diagnosis of temporal, frontal, or parietal lobe seizures. Lack of recognition of insular seizures may be responsible for some epilepsy surgery failures. METHODS: We retrospectively reviewed and analyzed MEG data in 14 patients with refractory insular seizures defined through intracranial electroencephalography (EEG) or by the presence of an epileptogenic lesion in the insula with compatible seizure semiology. MEG was performed as part of the noninvasive presurgical evaluation, using a 275-channel whole head MEG system. MEG data were analyzed using a single equivalent current dipole model. MEG localization was compared to interictal positron emission tomography (PET) and ictal single photon emission computed tomography (SPECT) results and to the resection margin. KEY FINDINGS: Three patterns of MEG spike sources were observed. Seven patients showed an anterior operculoinsular clusters and two patients had a posterior operculoinsular cluster. No spikes were detected in one patient, and the remaining four patients showed a diffuse perisylvian distribution. Spike sources showed uniform orientation perpendicular to the sylvian fissure. Nine patients proceeded to insular epilepsy surgery with favorable surgical outcome. Among patients with anterior operculoinsular cluster who proceeded to have surgery, MEG provided superior information to ictal SPECT in four of six patients and to interictal PET in five of six patients. SIGNIFICANCE: MEG is useful in identifying patients who are likely to benefit from epilepsy surgery targeting the insula, particularly if a tight dipole cluster is identified even if other noninvasive modalities fail to produce localizing results.

Language lateralization in individuals with callosal agenesis: an fMRI study.

Since the seminal work of Broca in 1861, it is well established that language is essentially processed in the left hemisphere. However, the origin of hemispheric specialization remains controversial. Some authors posit that language lateralization is genetically determined, while others have suggested that hemispheric specialization develops with age. Tenants of the latter view have further suggested that the adult pattern of left hemispheric specialization is achieved by means of callosal inhibition of homologous speech areas in the right hemisphere during ontogeny. According to this hypothesis, one would expect language to develop bilaterally in the acallosal brain. A recent functional magnetic resonance imaging (fMRI) study in one patient with agenesis of the corpus callosum suggests that this might indeed be the case (Riecker et al., 2007). However, given the large anatomic and functional variability in the population of subjects with agenesis of the corpus callosum, this finding needs to be more extensively replicated. In the present study, we explored language lateralization in six individuals with agenesis of the corpus callosum using an fMRI protocol which included a syntactic decision task and a sub-vocal verbal fluency task. Two neurologically intact control groups, one comparable to the acallosals in terms of IQ, age and education (n=6) and one group with a high IQ (n=5), performed the same tasks. No differences were found between language lateralization of the subjects with agenesis of the corpus callosum and the control groups in the receptive speech task. However, for expressive speech, the groups differed with respect to frontal activations, with the acallosal participants showing a more bilateral pattern of activation than the high-IQ participants only. No differences were found for temporal regions. Overall, these results indicate that the corpus callosum is not essential for the establishment of lateralized language functions.

Value of 3.0 T MR imaging in refractory partial epilepsy and negative 1.5 T MRI.

BACKGROUND: High-field 3.0 T MR scanners provide an improved signal-to-noise ratio which can be translated in higher image resolution, possibly allowing critical detection of subtle epileptogenic lesions missed on standard-field 1.0-1.5 T MRIs. In this study, the authors explore the potential value of re-imaging at 3.0 T patients with refractory partial epilepsy and negative 1.5 T MRI. METHODS: We retrospectively identified all patients with refractory partial epilepsy candidate for surgery who had undergone a 3.0 T MR study after a negative 1.5 T MR study. High-field 3.0 T MRIs were reviewed qualitatively by neuroradiologists experienced in interpreting epilepsy studies with access to clinical information. Relevance and impact on clinical management were assessed by an epileptologist. RESULTS: Between November 2006 and August 2009, 36 patients with refractory partial epilepsy candidate for surgery underwent 3.0 T MR study after a 1.5 T MR study failed to disclose a relevant epileptogenic lesion. A potential lesion was found only in two patients (5.6%, 95% CI: 1.5-18.1%). Both were found to have hippocampal atrophy congruent with other presurgical localization techniques which resulted in omission of an invasive EEG study and direct passage to surgery. CONCLUSIONS: The frequency of detection of a new lesion by re-imaging at 3.0 T patients with refractory partial epilepsy candidate for surgery was found to be low, but seems to offer the potential of a significant clinical impact for selected patients. This finding needs to be validated in a prospective controlled study.

Functional reorganization of the auditory pathways (or lack thereof) in callosal agenesis is predicted by monaural sound localization performance.

Neuroimaging studies show that permanent peripheral lesions such as unilateral deafness cause functional reorganization in the auditory pathways. However, functional reorganization of the auditory pathways as a result of higher-level damage or abnormalities remains poorly investigated. A relatively recent behavioural study points to functional changes in the auditory pathways in some, but interestingly not in all, of the acallosal individuals that were tested. The present study uses fMRI to investigate auditory activities in both cerebral hemispheres in those same acallosal subjects in order to directly investigate the contributions of ipsilateral and contralateral functional pathways reorganization. Predictions were made that functional reorganization could be predicted from behavioural performance. As reported previously in a number of neuroimaging studies, results showed that in neurologically intact subjects, binaural stimulation induced balanced activities between both hemispheres, while monaural stimulation induced strong contralateral activities and weak ipsilateral activities. In accordance with behavioural predictions, some acallosal subjects showed patterns of auditory cortical activities that were similar to those observed in neurologically intact subjects while others showed functional reorganization of the auditory pathways. Essentially they showed a significant increase and a significant decrease of neural activities in the contralateral and/or ipsilateral pathways, respectively. These findings indicate that at least in some acallosal subjects, functional reorganization inside the auditory pathways does contribute to compensate for the absence of the corpus callosum.

Global motion stimuli and form-from-motion stimuli: common characteristics and differential activation patterns.

We used functional Magnetic Resonance Imaging (fMRI) to explore the areas underlying the processing of two similar motion stimuli that evoke different types of processing. The results indicated that while form-from-motion (FFM) stimuli activated both lateral occipital complex (LOC) and MT complex (MT+), only the LOC remained significantly activated when contrasted with a global motion stimulus (GMS) with different coherence levels. Because of the large number of common characteristics shared between the stimuli, this contrast enabled us to isolate the regions implicated in form processing. The GMS on the other hand only activated MT+, reaching maximal intensity for low coherence. Overall, these data illustrate how two similar motion stimuli can elicit the participation of different cortical visual regions.

Revisiting the role of the insula in refractory partial epilepsy.

PURPOSE: Recent evidence suggesting that some epilepsy surgery failures could be related to unrecognized insular epilepsy have led us to lower our threshold to sample the insula with intracerebral electrodes. In this study, we report our experience resulting from this change in strategy. METHODS: During the period extending from October 2004 to June 2007, 18 patients had an intracranial study including 10 with insular coverage. The decision to sample the insula with intracerebral electrodes was made in the context of (1) nonlesional parietal lobe-like epilepsy; (2) nonlesional frontal lobe-like epilepsy; (3) nonlesional temporal lobe-like epilepsy; and (4) atypical temporal lobe-like epilepsy. RESULTS: Intracerebral recordings confirmed the presence of insular lobe seizures in four patients. Cortical stimulation performed in 9 of 10 patients with insular electrodes elicited, in decreasing order of frequency, somatosensory, viscerosensory, motor, auditory, vestibular, and speech symptoms. DISCUSSION: Our results suggest that insular cortex epilepsy may mimic temporal, frontal, and parietal lobe epilepsies and that a nonnegligeable proportion of surgical candidates with drug-resistant epilepsy have an epileptogenic zone that involves the insula.

Brain activity during emotionally negative pictures in schizophrenia with and without flat affect: an fMRI study.

The aim of this functional magnetic resonance imaging (fMRI) study was to compare regional brain activity in schizophrenia subjects with (FA+) and without (FA-) flat affect during the viewing of emotionally negative pictures. Thirteen FA+ subjects and 11 FA- subjects were scanned while being presented with a series of emotionally negative and neutral pictures. Experientially, the viewing of the negative pictures induced a negative emotional state whose intensity was significantly greater in the FA- group than in the FA+ group. Neurally, the Negative minus Neutral contrast revealed, in the FA- group, significant loci of activation in the midbrain, pons, anterior cingulate cortex, insula, ventrolateral orbitofrontal cortex, anterior temporal pole, amygdala, medial prefrontal cortex, and extrastriate visual cortex. In the FA+ group, this contrast produced significant loci of activation in the midbrain, pons, anterior temporal pole, and extrastriate visual cortex. When the brain activity measured in the FA+ group was subtracted from that measured in the FA- group, only the lingual gyrus was significantly activated. Perhaps in FA+ subjects an amygdaloid malfunction rendered the amygdala unable to correctly evaluate the emotional meaning of the pictures presented, thus preventing effective connectivity linking the amygdala to the brain regions implicated in the physiological and experiential dimensions of emotion. Alternatively, a disturbance of effective connectivity in the neural networks linking the midbrain and the medial prefrontal system may have been responsible for the quasi absence of emotional reaction in FA+ subjects, and the abnormal functioning of the medial prefrontal cortex and anterior cingulate cortex in the FA+ group.

Neural correlates of lexical and sublexical processes in reading.

The purpose of the present study was to compare the brain regions and systems that subserve lexical and sublexical processes in reading. In order to do so, three types of tasks were used: (i). silent reading of very high frequency regular words (lexical task); (ii). silent reading of nonwords (sublexical task); and, (iii). silent reading of very low frequency regular words (sublexical task). All three conditions were contrasted with a visual/phonological baseline condition. The lexical condition engaged primarily an area at the border of the left angular and supramarginal gyri. Activation found in this region suggests that this area may be involved in mapping orthographic-to-phonological whole word representations. Both sublexical conditions elicited significantly greater activation in the left inferior prefrontal gyrus. This region is thought to be associated with sublexical processes in reading such as grapheme-to-phoneme conversion, phoneme assembly and underlying verbal working memory processes. Activation in the left IFG was also associated with left superior and middle temporal activation. These areas are thought to be functionally correlated with the left IFG and to contribute to a phonologically based form of reading. The results as a whole demonstrate that lexical and sublexical processes in reading activate different regions within a complex network of brain structures.

The impact of individual differences on the neural circuitry underlying sadness.

Several functional neuroimaging studies have been carried out in healthy subjects to investigate the neural correlates of sadness. Importantly, there is little consistency among the results of these studies. Hypothesizing that individual differences may account for the discrepancies among these investigations, we conducted two functional magnetic resonance imaging (fMRI) studies to identify the neural circuitry underlying this basic emotion. In these two methodologically identical studies, two different groups (n = 10 for each study) of healthy female subjects were scanned while they were experiencing a transient state of sadness induced by viewing sad film excerpts. In the first of these studies, sadness was correlated with significant loci of activation in the anterior temporal pole and insula (P < 0.05, corrected). In the second study, however, sadness was correlated with significant activation in the orbitofrontal and medial prefrontal cortices (P < 0.05, corrected). In addition, individual statistical parametric maps revealed a marked degree of interindividual variability in both Study 1 and Study 2. These results strongly support the view that individual differences may be responsible for the inconsistencies found in the literature regarding the neural substrates of sadness and of other basic emotions. These findings also suggest that individual data should be reported in addition to group data, because they provide useful information about the variability present in the subjects investigated and, thus, about the typicality and generalizability of the results.

Separate neural circuits for primary emotions? Brain activity during self-induced sadness and happiness in professional actors.

The question of whether distinct or similar neural substrates underlie primary emotions has not been resolved yet. To address this issue, we used fMRI to scan professional actors during self-induced states of sadness and happiness. Results demonstrated that, relative to an emotionally Neutral state, both the Sad and the Happy states were associated with significant loci of activation, bilaterally, in the orbitofrontal cortex, and in the left medial prefrontal cortex, left ventrolateral prefrontal cortex, left anterior temporal pole, and right pons. These loci of activation were localized distinctly within these regions, that is, in different sub-regions. These results suggest that sadness and happiness may be associated with similar brain regions but distinct sub-regions and neural circuits.

Neural circuitry underlying voluntary suppression of sadness.

BACKGROUND: The ability to voluntarily self-regulate negative emotion is essential to a healthy psyche. Indeed, a chronic incapacity to suppress negative emotion might be a key factor in the genesis of depression and anxiety. Regarding the neural underpinnings of emotional self-regulation, a recent functional neuroimaging study carried out by our group has revealed that the dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex are involved in voluntary suppression of sexual arousal. As few things are known, still, with respect to the neural substrate underlying volitional self-regulation of basic emotions, here we used functional magnetic resonance imaging to identify the neural circuitry associated with the voluntary suppression of sadness. METHODS: Twenty healthy female subjects were scanned during a Sad condition and a Suppression condition. In the Sad condition, subjects were instructed to react normally to sad film excerpts whereas, in the Suppression condition, they were asked to voluntarily suppress any emotional reaction in response to comparable stimuli. RESULTS: Transient sadness was associated with significant loci of activation in the anterior temporal pole and the midbrain, bilaterally, as well as in the left amygdala, left insula, and right ventrolateral prefrontal cortex (VLPFC) (Brodmann area [BA] 47). Correlational analyses carried out between self-report ratings of sadness and regional blood oxygen level dependent (BOLD) signal changes revealed the existence of positive correlations in the right VLPFC (BA 47), bilaterally, as well as in the left insula and the affective division of the left anterior cingulate gyrus (BA 24/32). In the Suppression condition, significant loci of activation were noted in the right DLPFC (BA 9) and the right orbitofrontal cortex (OFC) (BA 11), and positive correlations were found between the self-report ratings of sadness and BOLD signal changes in the right OFC (BA 11) and right DLPFC (BA 9). CONCLUSIONS: These results confirm the key role played by the DLPFC in emotional self-regulation. They also indicate that the right DLPFC and right OFC are components of a neural circuit implicated in voluntary suppression of sadness.

"Change the mind and you change the brain": effects of cognitive-behavioral therapy on the neural correlates of spider phobia.

Questions pertaining to the neurobiological effects of psychotherapy are now considered among the most topical in psychiatry. With respect to this issue, positron emission tomography (PET) findings indicate that cognitive and behavioral modifications, occurring in a psychotherapeutic context, can lead to regional brain metabolic changes in patients with major depression or obsessive-compulsive disorder. The goal of the present functional magnetic resonance imaging (fMRI) study, which constitutes the first neuroimaging investigation of the effects of cognitive-behavioral therapy (CBT) using an emotional activation paradigm, was to probe the effects of CBT on the neural correlates of spider phobia. In order to do so, fMRI was used in subjects suffering from spider phobia (n = 12) to measure, before and after effective CBT, regional brain activity during the viewing of film excerpts depicting spiders. Normal control subjects were also scanned (once) while they were exposed to the same film excerpts. Results showed that, in phobic subjects before CBT, the transient state of fear triggered, during the viewing of the phobogenic stimuli, was correlated with significant activation of the right dorsolateral prefrontal cortex (Brodmann area-BA 10), the parahippocampal gyrus, and the visual associative cortical areas, bilaterally. For normal control subjects (n = 13), only the left middle occipital gyrus and the right inferior temporal gyrus were significantly activated. In phobic subjects before CBT, the activation of the dorsolateral prefrontal cortex (BA 10) may reflect the use of metacognitive strategies aimed at self-regulating the fear triggered by the spider film excerpts, whereas the parahippocampal activation might be related to an automatic reactivation of the contextual fear memory that led to the development of avoidance behavior and the maintenance of spider phobia. After successful completion of CBT, no significant activation was found in the dorsolateral prefrontal cortex (BA 10) or the parahippocampal gyrus. These findings suggest that a psychotherapeutic approach, such as CBT, has the potential to modify the dysfunctional neural circuitry associated with anxiety disorders. They further indicate that the changes made at the mind level, within a psychotherapeutic context, are able to functionally "rewire" the brain.

Areas of brain activation in males and females during viewing of erotic film excerpts.

Various lines of evidence indicate that men generally experience greater sexual arousal (SA) to erotic stimuli than women. Yet, little is known regarding the neurobiological processes underlying such a gender difference. To investigate this issue, functional magnetic resonance imaging was used to compare the neural correlates of SA in 20 male and 20 female subjects. Brain activity was measured while male and female subjects were viewing erotic film excerpts. Results showed that the level of perceived SA was significantly higher in male than in female subjects. When compared to viewing emotionally neutral film excerpts, viewing erotic film excerpts was associated, for both genders, with bilateral blood oxygen level dependent (BOLD) signal increases in the anterior cingulate, medial prefrontal, orbitofrontal, insular, and occipitotemporal cortices, as well as in the amygdala and the ventral striatum. Only for the group of male subjects was there evidence of a significant activation of the thalamus and hypothalamus, a sexually dimorphic area of the brain known to play a pivotal role in physiological arousal and sexual behavior. When directly compared between genders, hypothalamic activation was found to be significantly greater in male subjects. Furthermore, for male subjects only, the magnitude of hypothalamic activation was positively correlated with reported levels of SA. These findings reveal the existence of similarities and dissimilarities in the way the brain of both genders responds to erotic stimuli. They further suggest that the greater SA generally experienced by men, when viewing erotica, may be related to the functional gender difference found here with respect to the hypothalamus.