Characterization of atypical language activation patterns in focal epilepsy.

OBJECTIVE: Functional magnetic resonance imaging is sensitive to the variation in language network patterns. Large populations are needed to rigorously assess atypical patterns, which, even in neurological populations, are a minority. METHODS: We studied 220 patients with focal epilepsy and 118 healthy volunteers who performed an auditory description decision task. We compared a data-driven hierarchical clustering approach to the commonly used a priori laterality index (LI) threshold (LI < 0.20 as atypical) to classify language patterns within frontal and temporal regions of interest. We explored (n = 128) whether IQ varied with different language activation patterns. RESULTS: The rate of atypical language among healthy volunteers (2.5%) and patients (24.5%) agreed with previous studies; however, we found 6 patterns of atypical language: a symmetrically bilateral, 2 unilaterally crossed, and 3 right dominant patterns. There was high agreement between classification methods, yet the cluster analysis revealed novel correlations with clinical features. Beyond the established association of left-handedness, early seizure onset, and vascular pathology with atypical language, cluster analysis identified an association of handedness with frontal lateralization, early seizure onset with temporal lateralization, and left hemisphere focus with a unilateral right pattern. Intelligence quotient was not significantly different among patterns. INTERPRETATION: Language dominance is a continuum; however, our results demonstrate meaningful thresholds in classifying laterality. Atypical language patterns are less frequent but more variable than typical language patterns, posing challenges for accurate presurgical planning. Language dominance should be assessed on a regional rather than hemispheric basis, and clinical characteristics should inform evaluation of atypical language dominance. Reorganization of language is not uniformly detrimental to language functioning.

Amygdala opioid receptors mediate the electroacupuncture-induced deterioration of sleep disruptions in epilepsy rats.

BACKGROUND: Clinical and experimental evidence demonstrates that sleep and epilepsy reciprocally affect each other. Previous studies indicated that epilepsy alters sleep homeostasis; in contrast, sleep disturbance deteriorates epilepsy. If a therapy possesses both epilepsy suppression and sleep improvement, it would be the priority choice for seizure control. Effects of acupuncture of Feng-Chi (GB20) acupoints on epilepsy suppression and insomnia treatment have been documented in the ancient Chinese literature, Lingshu Jing (Classic of the Miraculous Pivot). Therefore, this study was designed to investigate the effect of electroacupuncture (EA) stimulation of bilateral Feng-Chi acupoints on sleep disruptions in rats with focal epilepsy. RESULTS: Our result indicates that administration of pilocarpine into the left central nucleus of amygdala (CeA) induced focal epilepsy and decreased both rapid eye movement (REM) sleep and non-REM (NREM) sleep. High-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints, in which a 30-min EA stimulation was performed before the dark period of the light:dark cycle in three consecutive days, further deteriorated pilocarpine-induced sleep disruptions. The EA-induced exacerbation of sleep disruption was blocked by microinjection of naloxone, µ- (naloxonazine), κ- (nor-binaltorphimine) or δ-receptor antagonists (natrindole) into the CeA, suggesting the involvement of amygdaloid opioid receptors. CONCLUSION: The present study suggests that high-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints exhibits no benefit in improving pilocarpine-induced sleep disruptions; in contrast, EA further deteriorated sleep disturbances. Opioid receptors in the CeA mediated EA-induced exacerbation of sleep disruptions in epileptic rats.

Activation of amygdala opioid receptors by electroacupuncture of Feng-Chi (GB20) acupoints exacerbates focal epilepsy.

BACKGROUND: The effect of seizure suppression by acupuncture of Feng-Chi (GB20) acupoints has been documented in the ancient Chinese literature, Lingshu Jing (Classic of the Miraculous Pivot), however, there is a lack of scientific evidence to prove it. This current study was designed to elucidate the effect of electroacupuncture (EA) stimulation of bilateral Feng-Chi (GB20) acupoints on the epileptic activity by employing an animal model of focal epilepsy. METHODS: Administration of pilocarpine into the left central nucleus of amygdala (CeA) induced the focal epilepsy in rats. Rats received a 30-min 100 Hz EA stimulation of bilateral Feng-Chi acupoints per day, beginning at 30 minutes before the dark period and performing in three consecutive days. The broad-spectrum opioid receptor antagonist (naloxone), µ-receptor antagonist (naloxonazine), δ-receptor antagonist (naltrindole) and κ-receptor antagonist (nor-binaltorphimine) were administered directly into the CeA to elucidate the involvement of CeA opioid receptors in the EA effect. RESULTS: High-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints did not suppress the pilocarpine-induced epileptiform electroencephalograms (EEGs), whereas it further increased the duration of epileptiform EEGs. We also observed that epilepsy occurred while 100 Hz EA stimulation of Feng-Chi acupoints was delivered into naïve rats. EA-induced augmentation of epileptic activity was blocked by microinjection of naloxone, µ- (naloxonazine), κ- (nor-binaltorphimine) or δ-receptor antagonists (natrindole) into the CeA, suggesting that activation of opioid receptors in the CeA mediates EA-exacerbated epilepsy. CONCLUSIONS: The present study suggests that high-frequency (100 Hz) EA stimulation of bilateral Feng-Chi acupoints has no effect to protect against pilocarpine-induced focal epilepsy; in contrast, EA further exacerbated focal epilepsy induced by pilocarpine. Opioid receptors in the CeA mediated EA-induced exacerbation of focal epilepsy.

SV2A protein is a broad-spectrum anticonvulsant target: functional correlation between protein binding and seizure protection in models of both partial and generalized epilepsy.

SV2A, a synaptic vesicle protein, has been recently identified as a binding target for levetiracetam (Keppra). The specific mechanism by which SV2A binding leads to seizure protection has not yet been fully elucidated. However, a functional correlation between SV2A binding affinity and anticonvulsant potency has been observed in the mouse audiogenic seizure model. The present study was undertaken to test whether similar correlations exist in rodent models of partial and generalized epilepsies. As expected, there was a high degree of correlation between anticonvulsant potency and SV2A binding affinity in the mouse audiogenic seizure model (r(2)=0.77; p<0.001). A similar correlation was also observed in the mouse corneal kindling (r(2)=0.80; p<0.01) and in the rat model of generalized absence epilepsy (GAERS) (r(2)=0.72; p<0.01). Moreover, there were no significant differences between the slopes and intercepts of regression lines in these models. Interestingly, the protective potencies in these three epilepsy models were also well correlated with each other. As such, protective doses of a given SV2A ligand in one model could be easily predicted based on the data obtained in another model. Taken together, these results support the concept that SV2A protein is an important target for both partial and generalized epilepsies and thereby relevant for the generation of new antiepileptic drugs with potential broad-spectrum efficacy.

Metabolic changes of subcortical structures in intractable focal epilepsy.

PURPOSE: Intractable focal epilepsy is commonly associated with cortical glucose hypometabolism on interictal 2-deoxy-2[18F]-fluoro-D-glucose (FDG) positron emission tomography (PET). However, subcortical brain structures also may show hypometabolism on PET and volume changes on magnetic resonance imaging (MRI) studies, and these are less well understood in terms of their pathophysiology and clinical significance. In the present study, we analyzed alterations of glucose metabolism in subcortical nuclei and hippocampus by using FDG-PET in young patients with intractable epilepsy. METHODS: Thirty-seven patients (mean age, 7.5 years; age range, 1-27 years) with intractable frontal (n = 23) and temporal (n = 14) lobe epilepsy underwent FDG-PET scanning as part of their presurgical evaluation. Normalized glucose metabolism was measured in the thalamus and caudate and lentiform nuclei, as well as in hippocampus, both ipsi- and contralateral to the epileptic focus, and correlated with duration and age at onset of epilepsy, presence or absence of secondary generalization, location of the epileptic focus, and extent of cortical glucose hypometabolism. RESULTS: Long duration of epilepsy was associated with lower glucose metabolism in the ipsilateral thalamus and hippocampus. Duration of epilepsy was a significant predictor of ipsilateral thalamic glucose metabolism in both temporal and frontal lobe epilepsy. Presence of secondarily generalized seizures also was associated with lower normalized metabolism in the ipsilateral thalamus and hippocampus. Extent of cortical hypometabolism did not correlate with subcortical metabolism, and glucose metabolism in the caudate and lentiform nuclei did not show any correlation with the clinical variables. CONCLUSIONS: The findings suggest that metabolic dysfunction of the thalamus ipsilateral to the seizure focus may become more severe with long-standing temporal and frontal lobe epilepsy, and also with secondary generalization of seizures.

Correlation between GABA(A) receptor density and vagus nerve stimulation in individuals with drug-resistant partial epilepsy.

Vagus nerve stimulation (VNS) is an important option for the treatment of drug-resistant epilepsy. Through delivery of a battery-supplied intermittent current, VNS protects against seizure development in a manner that correlates experimentally with electrophysiological modifications. However, the mechanism by which VNS inhibits seizures in humans remains unclear. The impairment of gamma-aminobutyric acid (GABA)-mediated neuronal inhibition associated with epilepsy has suggested that GABA(A) receptors might contribute to the therapeutic efficacy of VNS. We have now applied single photon emission computed tomography (SPECT) with the benzodiazepine receptor inverse agonist [123I]iomazenil to examine cortical GABA(A) receptor density (GRD) before and 1 year after implantation of a VNS device in 10 subjects with drug-resistant partial epilepsy. VNS therapeutic responses resulted significantly correlated with the normalization of GRD. Moreover, a comparable control group, scheduled for a possible VNS implant, failed to show significant GRD variations after 1 year of a stable anti-epileptic treatment. These results suggest that VNS may modulate the cortical excitability of brain areas associated with epileptogenesis and that GABA(A) receptor plasticity contributes to this effect.

Ion channels and epilepsy.

Ion channels provide the basis for the regulation of excitability in the central nervous system and in other excitable tissues such as skeletal and heart muscle. Consequently, mutations in ion channel encoding genes are found in a variety of inherited diseases associated with hyper- or hypoexcitability of the affected tissue, the so-called 'channelopathies.' An increasing number of epileptic syndromes belongs to this group of rare disorders: Autosomal dominant nocturnal frontal lobe epilepsy is caused by mutations in a neuronal nicotinic acetylcholine receptor (affected genes: CHRNA4, CHRNB2), benign familial neonatal convulsions by mutations in potassium channels constituting the M-current (KCNQ2, KCNQ3), generalized epilepsy with febrile seizures plus by mutations in subunits of the voltage-gated sodium channel or the GABA(A) receptor (SCN1B, SCN1A, GABRG2), and episodic ataxia type 1-which is associated with epilepsy in a few patients--by mutations within another voltage-gated potassium channel (KCNA1). These rare disorders provide interesting models to study the etiology and pathophysiology of disturbed excitability in molecular detail. On the basis of genetic and electrophysiologic studies of the channelopathies, novel therapeutic strategies can be developed, as has been shown recently for the antiepileptic drug retigabine activating neuronal KCNQ potassium channels.

Drug-induced changes in cerebral glucose consumption in bifrontal epilepsy.

PURPOSE: Positron emission tomography (PET) using 18F-radiolabeled deoxyglucose (18F-FDG) is a sensitive procedure for detection of epileptogenic foci. Although alterations in glucose consumption are not restricted to the area of seizure generation itself, the magnitude and extent of cerebral metabolic disturbances induced by epileptic discharges can be detected. Despite two decades of epilepsy research using 18F-FDG-PET, little is known about the metabolic changes during therapy of focal epilepsy. We report on a child with frontal epilepsy with severe glucose hypometabolism that was nearly completely normalized during drug therapy. METHODS: Interictal 18F-FDG-PET was performed at the onset of epilepsy and after optimized drug therapy in a 5-year-old boy with behavioral abnormalities and repetitive seizures of frontal origin with bifrontal interictal EEG slowing for 8 weeks. Both scans were anatomically matched; initial and intratherapeutic glucose metabolism were compared. RESULTS: In accordance with the epileptogenic focus as identified by EEG and ictal/interictal perfusion single-photon emission tomography (SPECT), bifrontal hypometabolism was depicted by 18F-FDG-PET. Magnetic resonance imaging (MRI) was unremarkable. After dual-drug therapy (valproate, carbamazepine), the boy became seizure free, and his initial behavioral deficits disappeared. A control PET study after 3 months of therapy showed restored glucose consumption; the frontal EEG slowing was normalized. CONCLUSIONS: This case demonstrates that reduction of glucose metabolism in epileptogenic foci may be a result of reversible neuronal dysfunction that correlates with the electroclinical follow-up.

Relation of interictal spike frequency to 1H-MRSI-measured NAA/Cr.

PURPOSE: Whereas EEG spiking and decreases of the neuronal marker N-acetyl-aspartate (NAA) both localize well the epileptic focus, the significance of the intensity of these variables is unclear. Therefore we investigated whether the frequency of interictal surface spikes is related to the degree of N-acetyl-aspartate/creatine (NAA/Cr) ratio decrease as measured by proton magnetic resonance (MR) spectroscopic imaging (1H-MRSI) in patients with intractable partial epilepsy. METHODS: We retrospectively studied 14 patients, nine with temporal lobe epilepsy and five with frontal lobe epilepsy. Spikes that occurred during prolonged video-EEG monitoring from electrodes placed according to the International 10-20 system were counted blinded to the 1H-MRSI results. Eight electrode positions (F3/4, C3/4, T3/4, T5/6) were assigned to underlying brain subregions in the 1H-MRSI volume of interest. We converted NAA/Cr ratios into z-scores (NAA/Cr(z)) to compared NAA/Cr values directly across subregions. We calculated Spearman rank-order (p) and Pearson product-moment (r) correlations between spike frequency and NAA/Cr(z) values overall, as well as within each brain subregion. RESULTS: We found an overall negative relation between spike-frequency data and NAA/Cr(z) data (p = -0.341). When analyzing only spiking subregions, this negative relation became slightly stronger (p = -0.442; r = -0.338). When data from the eight sites were considered separately, this negative relation remained in most instances. CONCLUSIONS: Our results reveal a trend toward higher interictal spike frequencies on surface EEG in regions of pronounced neuronal metabolic damage or dysfunction. This suggests that both variables parallel an underlying pathologic substrate, although the pathophysiologic processes may be distinct.

Regional age dependence of human brain metabolites from infancy to adulthood as detected by quantitative localized proton MRS.

Regional changes of metabolite concentrations during human brain development were assessed by quantitative localized proton magnetic resonance spectroscopy in vivo. Apart from measurements in young healthy adults, the study was based on regional spectra from 97 children who were either healthy or suffered from mental retardation, movement disorders, epilepsies, neoplasm, or vascular malformation. Metabolite quantitation focused on cortical gray and white matter, cerebellum, thalamus, and basal ganglia in six age groups from infancy to adulthood. During infancy and childhood, the concentration of the neuroaxonally located N-acetylasparate increased in gray matter, cerebellum, and thalamus, whereas a constant level was detected in white matter. These findings are in line with regional differences in the formation of synaptic connections during early development and suggest a role of N-acetylaspartate as a marker of functioning neuroaxonal tissue rather than of the mere presence of nerve cells. This view is further supported by high concentrations of taurine in gray matter and cerebellum during infancy, because taurine is also believed to be involved in the process of synapse formation. Remarkably, in basal ganglia both N-acetylaspartate and taurine remain constant at relatively high concentrations. Other metabolite changes during maturation include increases of N-acetylaspartylglutamate, especially in thalamus and white matter, and a decrease of glutamine in white matter. Despite regional differences and some small changes during the first year of life, the concentrations of creatine, phosphocreatine, choline-containing compounds, myoinositol, and glutamate remain constant afterward. The creatine to phosphocreatine concentration ratio yields 2:1 throughout the human brain irrespective of region or age. The observed increase of the proton resonance line-width with age is most pronounced in basal ganglia and corresponds to the age-related and tissue-dependent increase of brain iron.

Magnetic resonance spectroscopy in focal epilepsy: 31P and 1H spectroscopy.

Magnetic resonance spectroscopy (MRS) is rapidly becoming a clinical and research tool in epilepsy. Animal studies have demonstrated metabolic abnormalities in the interictal and ictal state showing energy depletion and changes in neuronal compounds. Similarly, clinical studies have demonstrated consistent abnormalities involving energy (31P) and cellular dependent (1H) compounds. Phosphorus MRS (31P) shows lateralizing metabolic dysfunction in approximately 65-75 p. 100 of patients with temporal lobe epilepsy (PCr/Pi). Proton MRS (1H) using single-voxel or chemical shift imaging has demonstrated a high sensitivity in lateralizing temporal lobe epilepsy (65-96 p. 100) with bilateral changes seen in 35-45 p. 100 of patients. The role of MRS in extra-temporal lobe epilepsy is less accurate because of the spatial limitations of current techniques. Further advances in this field promise to improve the clinical utility of MRS in epilepsy.

Relationship between seizure-induced transcription of the DNA damage-inducible gene GADD45, DNA fragmentation, and neuronal death in focally evoked limbic epilepsy.

We investigated the temporal and spatial profile of mRNA transcription for the growth arrest and DNA damage-inducible gene GADD45, DNA fragmentation, and neuronal death in rat brain following focally evoked limbic seizures. GADD45 mRNA was detected by in situ hybridization, whereas fragmented DNA was detected using in situ nick end-labeling by the large (Klenow) fragment of DNA polymerase I. Kainic acid (0.1 microg) was injected into the right amygdala of rats to induce seizures for 45 min, after which diazepam (30 mg/kg) was administered. GADD45 mRNA, DNA fragmentation, and cell death were quantified bilaterally within six limbic brain regions 0-96 h following seizure cessation. All animals underwent seizures of equivalent severity and duration as determined electrographically. In situ hybridization detected bilateral up-regulation of GADD45 mRNA throughout the CA1, CA3, and dentate gyrus of the hippocampus, the piriform and retrosplenial cortices, and the thalamus within 1 h of seizure termination. GADD45 mRNA levels remained elevated for up to 6 h, declining to baseline within all structures by 16 h. Klenow-positive cells were only found within the CA3 pyramidal layer of the ipsilateral hippocampus and appeared 16-72 h following seizure cessation. Morphologic cell death was also restricted to the CA3 subfield. These data demonstrate that focally evoked limbic seizures trigger early bihemispheric GADD45 mRNA transcription within connected limbic structures, whereas subsequent DNA fragmentation and cell death are restricted to selectively vulnerable brain regions.

Thalamocortical circuits causing remote hypometabolism during focal interictal epilepsy.

The functional circuit causing depression of cerebral glucose metabolism in brain areas remote from an epileptic focus was investigated in experiments on the cortex of the rat. Epileptic activity was induced by direct epicortical application of Na-penicillin onto the motor cortical area Fr1/Fr2. The increased neuronal activity was associated with an increase of metabolism in the focal area and a decrease in somatosensory cortical areas. Metabolism was also massively increased in the thalamus, predominantly in the posterior nucleus. Stereotactic radiofrequency lesioning of this nucleus, 30 days prior to the induction of the epileptic focus, restricted the area with increase of metabolism to the upper cortical laminae, and abolished the cortical hypometabolism in the sensory cortex. It is suggested that the primary functional circuit affected by the acute epileptic focus in the present model consists of the motor cortex, the thalamic nucleus posterior and the somatosensory cortex.

Proton magnetic resonance spectroscopic imaging in patients with extratemporal epilepsy.

PURPOSE: Reduced levels of N-acetylaspartate (NAA) in temporal lobes responsible for temporal lobe epilepsy have been observed consistently in proton magnetic resonance spectroscopy (MRS) studies. METHODS: We investigated the potential of proton MRS to detect low NAA outside of the temporal lobes in patients with non-lesional partial extratemporal epilepsy. Proton MR spectroscopic imaging (MRSI) data of both frontal lobes and central/postcentral regions were obtained in 20 such patients and 16 normal control subjects. The epileptogenic region was determined by an extensive clinical-EEG investigation, including the recording of habitual seizures in each patient, and intracranial EEG recordings in 10 patients. RESULTS: The relative NAA resonance intensities (i.e., NAA/phosphocreatine plus creatine (CR(t)), NAA/choline-containing metabolites (Cho(t)) and NAA/Cr(t) + Cho(t)), were all significantly reduced throughout the spectroscopic image as compared with that of the controls. Furthermore, reduction of the NAA ratios was greater in the epileptogenic region as compared with the nonepileptogenic regions, on EEG investigation. CONCLUSIONS: In vivo proton MRSI of patients with nonlesional partial extratemporal epilepsy detected evidence of widespread neuronal damage or dysfunction that was greatest in the region of seizure focus.

Hippocampal N-acetylaspartate in neocortical epilepsy and mesial temporal lobe epilepsy.

Previous magnetic resonance spectroscopy (MRS) studies have shown that N-acetylaspartate (NAA) is reduced not only in the ipsilateral but also in the contralateral hippocampus of many patients with mesial temporal lobe epilepsy (mTLE). The reason for the contralateral damage is not clear. To test whether the hippocampus is also damaged if the focus is outside the hippocampus, we have measured patients with neocortical epilepsy (NE). Therefore, the goals of this study were to determine if hippocampal NAA is reduced in NE and if hippocampal NAA discriminates NE from mTLE. MRS imaging (MRSI) studies were performed on 10 NE patients and compared with MRSI results in 23 unilateral mTLE patients and 16 controls. The results show that, in contrast to mTLE, NAA was not reduced in the hippocampus of NE patients, neither ipsilateral nor contralateral to the seizure focus. These results suggest that repeated seizures do not cause secondary damage to the hippocampus. The absence of spectroscopic differences in NE may help to distinguish NE from mTLE.

Coupling of cortical and thalamic metabolism in experimentally induced visual and somatosensory focal epilepsy.

Focal epileptic activity induces widespread metabolic disturbances beyond the area of the electroencephalographically detectable focus. In order to find out whether the metabolic coupling between the epileptic focus and other brain regions depends on the localization of the focus, two groups of rats with epileptic foci at different sites were investigated. In the first group acute epileptic activity was induced by application of penicillin to the secondary visual cortex (Oc2), and in the second group to the primary somatosensory cortex (Par1). Metabolism was analyzed using the [14C]deoxyglucose autoradiographic method. In both groups of animals, hypermetabolism in the area of the focus and in specific functionally coupled thalamic nuclei was observed. Focal epileptic activity in the secondary visual cortex induced significant hypometabolism in remote ipsilateral cortical areas. In rats with epileptic foci in the primary somatosensory cortex hypometabolism in extrafocal ipsilateral cortical areas was less prominent. These findings provide further support for the integral involvement of the thalamus in modulating metabolism in remote cortical brain regions during focal epileptic activity. The extent of metabolic alterations may depend on the site of the epileptic focus and the connectivity of the recruited thalamic nuclei.

Widespread functional deficits in perception-related networks demonstrated by PET in a case with simple visual seizures.

PURPOSE: To study benzodiazepine receptor (BZR) density and functional deficits in occipital lobe epilepsy. METHODS: A 39-year-old man who had simple partial visual seizures after neurosurgical transtentorial extirpation of a pinealoma was studied by EEG, magnetic resonance imaging (MRI), and positron emission tomography (PET) of [18F]2-fluoro-2-deoxy-D-glucose (FDG) at rest and during visual activation task and[11C]flumazenil (FMZ). RESULTS: Electroencephalographic recordings were nonspecific, and MRI did not reveal any morphologic anomaly in the occipital lobe. Flumazenil-PET demonstrated a small epileptogenic region in the right visual association cortex and FDG-PET showed hypometabolism in a corresponding location and thalamic diaschisis. Stimulation of occipital metabolism by a continuous visual recognition task improved significantly the contrast between the dysfunctional zone and its surround. CONCLUSIONS: As BZR deficits are restricted to a small region, widespread hypometabolism in networks involved in visual information processing indicates an extensive functional deactivation by the epileptogenic focus.

Coupling of cortical and thalamic ictal activity in human partial epilepsy: demonstration by functional magnetic resonance imaging.

PURPOSE: To localize metabolic coupling between a cortical seizure focus and other brain regions by using functional magnetic resonance imaging (fMRI) data of ictal events obtained in a patient with frequent partial seizures involving his right face. METHODS: Cross-correlation analysis was used to examine time-dependent alterations in regional signal intensity that correlated with signal-intensity changes from a well-characterized cortical seizure focus in a patient with frequent partial seizures. RESULTS: Signal changes in the left ventrolateral thalamus showed a high degree of temporal correlation with signal changes in the left frontal cortical seizure focus, demonstrating close corticothalamic coupling of metabolism. CONCLUSIONS: A significant role for thalamocortical interactions in the pathophysiology of epilepsy has been suggested by studies in animal models and human patients. This finding provides further support for the integral involvement of the thalamus in human focal epilepsy and underscores the potential for identifying neuronal networks by using cross-correlation analysis of fMRI data.

Magnetic resonance spectroscopy.

Magnetic resonance spectroscopy, like PET, allows cerebral function to be assessed neuro-anatomically. In addition to being noninvasive and not requiring ionizing radiation, this technique can be performed with equipment available at most medical centers. Initial studies suggest both proton and phosphorous spectroscopy will be useful adjunctive presurgical tests for the localization of the epileptogenic foci in patients with partial epilepsy, especially those with extratemporal foci. Furthermore, MRS imaging may prove to be a useful tool for studying the response to medical treatment and the pathophysiologic basis of epilepsy.