FMRI of brain activation in a genetic rat model of absence seizures

PURPOSE: EEG-triggered functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during spontaneous spike-and-wave discharges (SWDs) in an epileptic rat strain under awake conditions. METHODS: Spontaneous absence seizures from 10 WAG/Rij rats were imaged by using T2*-weighted echo planar imaging at 4.7 Tesla. fMRI of the blood-oxygenation-level-dependent (BOLD) signal was triggered based on EEG recordings during imaging. Images obtained during spontaneous SWDs were compared with baseline images. RESULTS: Significant positive BOLD signal changes were apparent in several areas of the cortex and several important nuclei of the thalamus. In addition, no negative BOLD signal was found in any brain area. CONCLUSIONS: We have shown that EEG-triggered BOLD fMRI can be used to detect cortical and thalamic activation related to the spontaneous SWDs that characterize absence seizures in awake WAG/Rij rats. These results draw an anatomic correlation between areas in which increased BOLD signal is found and those in which SWDs have been recorded. In addition, no negative BOLD signal was found to be associated with these spontaneous SWDs. We also demonstrated the technical feasibility of using EEG-triggered fMRI in a genetic rat model of absence seizure.     

fMRI of generalized absence status epilepticus in conscious marmoset monkeys reveals corticothalamic activation

PURPOSE: A nonhuman primate model of generalized absence status epilepticus was developed for use in functional magnetic resonance imaging (fMRI) experiments to elucidate the brain mechanisms underlying this disorder. METHODS: Adult male marmoset monkeys (Callithrix jacchus) were treated with gamma-butyrolactone (GBL) to induce prolonged absence seizures, and the resulting spike-wave discharges (SWDs) were analyzed to determine the similarity to the 3-Hz SWDs that characterize the disorder. In addition, blood-oxygenation-level-dependent (BOLD) fMRI was measured at 4.7 Tesla after absence seizure induction with GBL. RESULTS: Electroencephalographic recordings during imaging showed 3-Hz SWDs typical of human absence seizures. This synchronized EEG pattern started within 15 to 20 min of drug administration and persisted for >60 min. In addition, pretreatment with the antiepileptic drug, ethosuximide (ESM), blocked the behavioral and EEG changes caused by GBL. Changes in BOLD signal intensity in the thalamus and sensorimotor cortex correlated with the onset of 3-Hz SWDs. The change in BOLD signal intensity was bilateral but heterogeneous, affecting some brain areas more than others. No significant negative BOLD changes were seen. CONCLUSIONS: The BOLD fMRI data obtained in this marmoset monkey model of absence status epilepticus shows activation within the thalamus and cortex.     

Simultaneous EEG-fMRI in drug-naive children with newly diagnosed absence epilepsy

Purpose: In patients with idiopathic generalized epilepsy (IGE), blood oxygen level dependent (BOLD) EEG during functional MRI (EEG‐fMRI) has been successfully used to link changes in regional neuronal activity to the occurrence of generalized spike‐and‐wave (GSW) discharges. Most EEG‐fMRI studies have been performed on adult patients with long‐standing epilepsy who were on antiepileptic medication. Here, we applied EEG‐fMRI to investigate BOLD signal changes during absence seizures in children with newly diagnosed childhood absence epilepsy (CAE). Methods: Ten drug‐naive children with newly diagnosed CAE underwent simultaneous EEG‐fMRI. BOLD signal changes associated with ictal EEG activity (i.e., periods of three per second GSW) were analyzed in predefined regions‐of‐interests (ROIs), including the thalamus, the precuneus, and caudate nucleus. Results: In 6 out of 10 children, EEG recordings showed periods of three per second GSW during fMRI. Three per second GSW were associated with regional BOLD signal decreases in parietal areas, precuneus, and caudate nucleus along with a bilateral increase in the BOLD signal in the medial thalamus. Taking into account the normal delay in the hemodynamic response, temporal analysis showed that the onset of BOLD signal changes coincided with the onset of GSW. Discussion: In drug‐naive individuals with CAE, ictal three per second GSW are associated with BOLD signal changes in the same striato‐thalamo‐cortical network that changes its regional activity during primary and secondary generalized paroxysms in treated adults. No BOLD signal changes in the striato‐thalamo‐cortical network preceded the onset of three per second GSW in unmediated children with CAE.     

Global and focal aspects of absence epilepsy: the contribution of genetic models

The cortico-reticular theory of absence epilepsy explains the origin of the bilateral generalized spike-wave discharges (SWDs) characterizing absence seizures via a subcortical pacemaker that is responsible for both normal sleep spindles and pathological SWDs. This pacemaker is the reticular thalamic nucleus (RTN); it produces spontaneous oscillations together with thalamic relay cells and the cortex in an assembled thalamo-cortico-thalamic network. Recently, Meeren et al. [2002. Cortical focus drives widespread corticothalamic networks during spontaneous absence seizures in rats. Journal of Neuroscience 22, 1480-1495.] proposed a focal theory of absence epilepsy based on experimental findings in the WAG/Rij rat, a genetic model of absence epilepsy: the somatosensory cortex contains a focus that initiates a cascade of events that ultimately leads to the occurrence of the bilateral and generalized SWDs if the state of the thalamo-cortical circuitry is favorable. Pharmacological, neurochemical, and neurophysiological data are presented and reviewed here that suggest SWDs might emerge from spontaneous oscillating neurons in the somatosensory cortex during both wakefulness and drowsiness. There is evidence for a variety of neurobiological changes, including a deficient global (parvalbumin) and local GABA-ergic (neurophysiological) system in the neocortex, which may explain why specifically the perioral region of the somatosensory cortex is hyperexcitable and the initiation site of 10Hz oscillations. The neuronal cortical and subcortical circuitry that produces SWDs is part of a large oscillatory system involved in generating cerebral rhythms associated with vibrissal movements. It needs to be established whether similar or comparable pathophysiological processes are also present in humans. Our hypothesis can be readily tested in other models and in humans considering that it is very specific and can be subjected to experimental verification.     

Impairment of Consciousness During Epileptic Seizures with Special Reference to Neuronal Mechanisms

Summary: Two neuronal structures, i.e., the cerebral cortex and the subcortical structures, were shown by clinical observations to be involved in maintaining consciousness. The alteration of consciousness during epileptic seizures is discussed with respect to these findings: Alterations of consciousness during epileptic seizures may be produced by subcortical, i.e., reticular formation, and/or cortical dysfunction followed by excessive, hypersynchronous neuronal discharges. An impairment of consciousness during absence seizures may be due mainly to cortical dysfunction; during complex partial seizures (CPS), it may be due to dysfunctional subcortical neuronal structures. The mechanisms underlying an alteration of consciousness are defined as causing "irritative" functional disturbances and/or as having "inhibitory" effects on consciousness-related structures.     

Relations between cortical and thalamic cellular activities during absence seizures in rats

In a rat model of generalized absence epilepsies (Genetic Absence Epilepsy Rats from Strasbourg, GAERS), multiunit activity was recorded simultaneously at different sites of the thalamocortical system under neurolept anaesthesia (fentanyl-droperidol). Under these conditions, bilaterally synchronized spike-and-wave-discharges (SWDs) occurred spontaneously on the electroencephalogram (EEG) that were in principle identical to those reported earlier from unanaesthetized preparations. The generation of SWDs on the EEG was associated with spike-concurrent, rhythmic burst-like activity in (mono-)synaptically connected regions of specific (somatosensory) thalamic regions and layers IV/V of the somatosensory cortex, and the reticular thalamic nucleus. Precursor activity was typically recorded in cortical units, concomitant with ‘embryonic’ SW seizures on the EEG, before the paroxysm was evident on the gross EEG and in the thalamus. On average, SWD-correlated activity in layers IV/V of the somatosensory cortex started significantly earlier than correlated burst-like firing in reticular and in ventrobasal thalamic neurons. Cellular peak firing in thalamus and cortex during bilaterally synchronized SWDs was related to the spike component on the gross EEG with the temporal rank order ventroposteromedial > ventrolateral ≥ ventroposterolateral thalamic > > rostral reticular thalamic nuclei ≥ cortex (layers IV/V) = caudal reticular thalamic nucleus. A spike-related depression and wave-related increase in firing was recorded in anteroventral ventrolateral thalamic areas, presumably reflecting their peculiar anatomical arrangement within the thalamus. These results from an in vivo preparation with intact synaptic connections that spontaneously produces SWDs indicate that SWDs spread within the thalamocortical network, involving short and long delays. The order of concurrent rhythmic firing observed in thalamocortical circuits during SW seizures are supportive of the hypothesis that the processes of rhythmogenesis recruit local thalamic networks, while cortical mechanisms appear to synchronize rhythmic activities on a larger spatiotemporal scale, thereby providing an important contribution to the generalization of epileptiform activity and expression of SWDs on the EEG.     

Ictal SPECT findings in typical absence seizures

Single photon emission computed tomography (SPECT) is known to reveal localized hyperperfusion during partial seizures, but is rarely performed in idiopathic generalized epilepsies. We report the ictal SPECT findings in a typical absence seizure. This 35-year-old woman with childhood absence epilepsy underwent prolonged electroencephalogram (EEG)-video monitoring, during which many stereotyped typical absence seizures were recorded. These consisted of brief staring spells with arrest of activity, associated with generalized 3 Hz spike-wave complexes on EEG. Following intravenous (i.v.) injection of 17.6 millicuries of Tc-99m Bicisate, SPECT was performed. The injection was performed during hyperventilation that induced a typical absence. Compared to the baseline SPECT scan that was normal, the ictal scan showed a generalized reduction in cortical activity. These findings do not support the “cortical” theory of typical absence seizures and the genesis of the 3 Hz spike-wave complexes. They may indeed support the subcortical or “centrencephalic” hypothesis.     

Rhythmic neuronal activity in S2 somatosensory and insular cortices contribute to the initiation of absence‐related spike‐and‐wave discharges

Purpose: The origin of bilateral synchronous spike‐and‐wave discharges (SWDs) that underlie absence seizures has been widely debated. Studies in genetic rodent models suggest that SWDs originate from a restricted region in the somatosensory cortex. The properties of this initiation site remain unknown. Our goal was to characterize the interictal, preictal and ictal neuronal activity in the primary and secondary cortical regions (S1, S2) and in the adjacent insular cortex (IC) in Genetic Absence Epilepsy Rats from Strasbourg (GAERS). Methods: We performed electroencephalography (EEG) recordings in combination with multisite local field potential (LFP) and single cell juxtacellular recordings, and cortical electrical stimulations, in freely moving rats and those under neurolept‐anesthesia. Key Findings: The onset of the SWDs was preceded by 5–9 Hz field potential oscillations, which were detected earlier in S2 and IC than in S1. Sustained SWDs could be triggered by a 2‐s train of 7‐Hz electrical stimuli at a lower current intensity in S2 than in S1. In S2 and IC, subsets of neurons displayed rhythmic firing (5–9 Hz) in between seizures. S2 and IC layers V and VI neurons fired during the same time window, whereas in S1 layer VI, neurons fired before layer V neurons. Just before the spike component of each SW complex, short‐lasting high‐frequency oscillations consistently occurred in IC ～20 msec before S1. Significance: Our findings demonstrate that the S2/IC cortical areas are a critical component of the macro‐network that is responsible for the generation of absence‐related SWDs.     

Involvement of the Thalamocortical System in Epileptic Loss of Consciousness

Summary: Experiments on putative neuronal mechanisms underlying absence seizures as well as clinical observations are critically reviewed for their ability to explain apparent "loss of consciousness." It is argued that the initial defect in absences lies with corticothalamic (CT) neuronal mechanisms responsible for selective attention and/or planning for action, rather than with those establishing either the states or the contents of consciousness. Normally, rich thalamocortical (TC)–CT feedback loops regulate the flow of information to the cortex and help its neurons to organize themselves in discrete assemblies, which through high-frequency (>30 Hz) oscillations bind those distributed processes of the brain that are considered important, so that we are able to focus on what is needed from moment to moment and be aware of this fact. This ability is transiently lost in absence seizures, because large numbers of CT loops are recruited for seconds in much stronger, low-frequency (∼3 Hz) oscillations of EPSP/IPSP sequences, which underlie electroencephalographic (EEG) spike-and-wave discharges (SWDs). These oscillations probably result from a transformation of the normal EEG rhythm of sleep spindles on an abnormal increase of cortical excitability that results in strong activation of inhibitory neurons in the cortex and in nucleus reticularis thalami. The strong general enhancement of CT feedback during SWDs may disallow the discrete feedback, which normally selects specific TC circuits for conscious perception and/or motor reaction. Such a mechanism of SWD generation allows variability in the extent to which different TC sectors are engaged in the SWD activity and thus explains the variable ability of some patients to respond during an absence, depending on the sensory modality examined.     

Thalamic atrophy in childhood absence epilepsy

PURPOSE: Patients with childhood absence epilepsy (CAE) have normal clinical magnetic resonance imaging (MRI) studies. The presence of abnormalities in corticothalamic networks has been suggested to be the functional basis of absence seizure generation. We assessed whether structural grey and white matter volume changes of these areas occurred in patients with absence seizures by using optimized voxel-based morphometry (VBM). METHODS: We recruited 13 patients with a clinical and EEG diagnosis of CAE (mean age at examination, 17 +/- 8 years) and compared them with a consecutive series of 109 controls (mean age, 29 +/- 9 years). The 3 tesla MRI examination included a 3D T(1)-weighted sequence, which was analyzed with an optimized VBM protocol using the SPM2 package. The threshold was set at p < 0.05, corrected for multiple comparisons. RESULTS: Compared with controls, CAE patients showed areas of grey matter decrease in both thalami and in the subcallosal gyrus. White matter decrease was found in the extranuclear subcortical area and in the white matter of the basal forebrain. Grey and white matter increase was restricted to small clusters of cortical and subcortical areas. CONCLUSIONS: Evidence exists of subcortical grey and white matter volume reduction in CAE patients. Bilateral thalamic atrophy may be either a result of damage from seizures (as in hippocampal sclerosis) or a reflection of a primary underlying pathology as the cause of absence seizures.     

Low frequency BOLD fluctuations during resting wakefulness and light sleep: a simultaneous EEG-fMRI study

Recent blood oxygenation level dependent functional MRI (BOLD fMRI) studies of the human brain have shown that in the absence of external stimuli, activity persists in the form of distinct patterns of temporally correlated signal fluctuations. In this work, we investigated the spontaneous BOLD signal fluctuations during states of reduced consciousness such as drowsiness and sleep. For this purpose, we performed BOLD fMRI on normal subjects during varying levels of consciousness, from resting wakefulness to light (non-slow wave) sleep. Depth of sleep was determined based on concurrently acquired EEG data. During light sleep, significant increases in the fluctuation level of the BOLD signal were observed in several cortical areas, among which visual cortex was the most significant. Correlations among brain regions involved with the default-mode network persisted during light sleep. These results suggest that activity in areas such as the default-mode network and primary sensory cortex, as measured from BOLD fMRI fluctuations, does not require a level of consciousness typical of wakefulness.     

Onset and propagation of spike and slow wave discharges in human absence epilepsy: A MEG study

Purpose: A nonlinear association and a source localization technique were used to describe the onset and propagation of spike‐and‐slow‐wave discharges (SWDs) in children with absence seizures. Previous studies have emphasized a leading cortical role in the generation of absence seizures in genetic epileptic rats. Methods: Synchronization between all magnetoencephalography (MEG) sensor‐couples before and during SWDs in five patients was investigated over time. A source localization [beamformer, SAM(g₂)] technique was used to find brain regions associated with the origin of the spikes of the SWDs. Results: The onset of SWDs was characterized by high associations at left and right frontal regions. An alternating pattern of high synchronization was found during trains of SWDs: generalized during the wave and localized during the spike; the origin of the spike was different from the onset of SWDs, more frontal lateral and medial parietal. The localization of this latter region was confirmed with SAM(g₂). Discussion: The outcome of the nonlinear association techniques demonstrated that SWDs have a local cortical onset, whereas the association and beamformer technique support a local or even a focal cortical involvement in the occurrence of the spike in a train of SWDs. In all, the cortex contains local frontal and parietal sites relevant before the onset of the generalized pattern of SWDs and other ones that might contain the driving force behind the spike in trains of 3–4 Hz SWDs.     

Altered resting‐state connectivity during interictal generalized spike‐wave discharges in drug‐naïve childhood absence epilepsy

Purpose: To investigate the intrinsic brain connections at the time of interictal generalized spike‐wave discharges (GSWDs) to understand their mechanism of effect on brain function in untreated childhood absence epilepsy (CAE). Methods: The EEG‐functional MRI (fMRI) was used to measure the resting state functional connectivity during interictal GSWDs in drug‐naïve CAE, and three different brain networks—the default mode network (DMN), cognitive control network (CCN), and affective network (AN)—were investigated. Results: Cross‐correlation functional connectivity analysis with priori seed revealed decreased functional connectivity within each of these three networks in the CAE patients during interictal GSWDS. It included precuneus‐dorsolateral prefrontal cortex (DLPFC), dorsomedial prefrontal cortex (DMPFC), and inferior parietal lobule in the DMN; DLPFC‐inferior frontal junction (IFJ), and pre‐supplementary motor area (pre‐SMA) subregions connectivity disruption in CCN; ACC‐ventrolateral prefrontal cortex (VLPFC) and DMPFC in AN; There were also some regions, primarily the parahippcampus, paracentral in AN, and the left frontal mid orb in the CCN, which showed increased connectivity. Conclusions: The current findings demonstrate significant alterations of resting‐state networks in drug naïve CAE subjects during interictal GSWDs and interictal GSWDs can cause dysfunction in specific networks important for psychosocial function. Impairment of these networks may cause deficits both during and between seizures. Our study may contribute to the understanding of neuro‐pathophysiological mechanism of psychosocial function impairments in patients with CAE. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Representation and propagation of epileptic activity in absences and generalized photoparoxysmal responses

Although functional imaging studies described networks associated with generalized epileptic activity, propagation patterns within these networks are not clear. In this study, electroencephalogram (EEG)‐based coherent source imaging dynamic imaging of coherent sources (DICS) was applied to different types of generalized epileptiform discharges, namely absence seizures (10 patients) and photoparoxysmal responses (PPR) (eight patients) to describe the representation and propagation of these discharges in the brain. The results of electrical source imaging were compared to EEG‐functional magnetic resonance imaging (fMRI) which had been obtained from the same data sets of simultaneous EEG and fMRI recordings. Similar networks were described by DICS and fMRI: (1) absence seizures were associated with thalamic involvement in all patients. Concordant results were also found for brain areas of the default mode network and the occipital cortex. (2) Both DICS and fMRI identified the occipital, parietal, and the frontal cortex in a network associated with PPR. (3) However, only when PPR preceded a generalized tonic‐clonic seizure, the thalamus was involved in the generation of PPR as shown by both imaging techniques. Partial directed coherence suggested that during absences, the thalamus acts as a pacemaker while PPR could be explained by a cortical propagation from the occipital cortex via the parietal cortex to the frontal cortex. In conclusion, the electrical source imaging is not only able to describe similar neuronal networks as revealed by fMRI, including deep sources of neuronal activity such as the thalamus, but also demonstrates interactions interactions within these networks and sheds light on pathogenetic mechanisms of absence seizures and PPR. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.     

Are absences truly generalized seizures or partial seizures originating from or predominantly involving the pre-motor areas? Some clinical and theoretical observations and their implications for seizure classification

In both the current (1981) ILAE Classification of Epileptic Seizures and the recently Proposed Diagnostic Scheme for People with Epilepsy and Epileptic Seizures, typical absence seizures are defined as generalized seizures, implying widespread subcortical and cortical neuronal involvement from onset with impairment of consciousness as the clinical hallmark. Clinical observations from three patients and clinical and experimental data from the literature suggest, however, that: (1) consciousness is retained in many typical absences; (2) the true hallmark of these seizures is arrest of motor initiation due to disturbance of pre-motor area frontal-lobe function; (3) typical absences and partial seizures from these areas may show similar clinical and EEG features and involve the same neuronal circuits. The neuronal system primarily involved in these seizures consists of a relatively limited cortico-thalamo-cortical circuit, including the reticular thalamic nucleus, the thalamocortical relay and the predominantly anterior and mesial frontal cerebral cortex, with the cortex probably acting as the primary driving site. Typical absences thus should not be classified or defined as generalized seizures, particularly since neuropathological and imaging studies increasingly argue for localized structural abnormalities, even in idiopathic or primary generalized epilepsy. These observations further highlight the intrinsic weaknesses of the current classification system for seizures and support further adaptations of the diagnostic system currently under development.     

Dynamic fMRI and EEG recordings during spike-wave seizures and generalized tonic-clonic seizures in WAG/Rij rats.

Generalized epileptic seizures produce widespread physiological changes in the brain. Recent studies suggest that "generalized" seizures may not involve the whole brain homogeneously. For example, electrophysiological recordings in WAG/Rij rats, an established model of human absence seizures, have shown that spike-and-wave discharges are most intense in the perioral somatosensory cortex and thalamus, but spare the occipital cortex. Is this heterogeneous increased neuronal activity matched by changes in local cerebral blood flow sufficient to meet or exceed cerebral oxygen consumption? To investigate this, we performed blood oxygen level-dependent functional magnetic resonance imaging (fMRI) measurements at 7T with simultaneous electroencephalogram recordings. During spontaneous spike-wave seizures in WAG/Rij rats under fentanylhaloperidol anesthesia, we found increased fMRI signals in focal regions including the perioral somatosensory cortex, known to be intensely involved during seizures, whereas the occipital cortex was spared. For comparison, we also studied bicuculline-induced generalized tonic-clonic seizures under the same conditions, and found fMRI increases to be larger and more widespread than during spike-and-wave seizures. These findings suggest that even in regions with intense neuronal activity during epileptic seizures, oxygen delivery exceeds metabolic needs, enabling fMRI to be used for investigation of dynamic cortical and subcortical network involvement in this disorder.     

Effect of intracranial administration of ethosuximide in rats with spontaneous or pentylenetetrazol-induced spike-wave discharges

Purpose: Generalized absence seizures are characterized by bilateral spike‐wave discharges (SWDs), particularly in the frontoparietal cortical region. In WAG/Rij and GAERS rats with absence epilepsy, recent evidence indicates that SWDs arise first from the lateral somatosensory cortex (LSC), that is, the cortical focus theory. To further understand the cortical role in SWD generation, two epileptic rat models were assessed. Methods: Two models, Long‐Evans rats with spontaneous SWDs and Wistar rats with low‐dose pentylenetetrazol‐induced SWDs (20 mg/kg, i.p.), were administered intracortical or intrathalamic ethosuximide (ESM) or saline. Electroencephalographic recordings were analyzed before and after intracranial microinfusion to evaluate onset, frequency, and duration of SWDs. Key Findings: In both epileptic rat models, ESM in the LSC significantly reduced SWD number, shortened SWD duration, and delayed SWD onset compared to saline. By contrast, ESM in the medial somatosensory cortex had little effect compared to saline. Intrathalamic infusion of ESM only delayed SWD onset. Significance: These findings suggest that the LSC may be essential for the occurrence of SWDs. Our data support the cortical focus theory for the generation of absence seizures.     

The role of subcortical structures in human epilepsy

Like normal cerebral function, epileptic seizures involve widespread network interactions between cortical and subcortical structures. Although the cortex is often emphasized as the site of seizure origin, accumulating evidence points to a crucial role for subcortical structures in behavioral manifestations, propagation, and, in some cases, initiation of epileptic seizures. Extensive previous studies have shown the importance of subcortical structures in animal seizure models, but corresponding human studies have been relatively few. We review the existing evidence supporting the importance of the thalamus, basal ganglia, hypothalamus, cerebellum, and brain stem in human epilepsy. We also propose a "network inhibition hypothesis" through which focal cortical seizures disrupt function in subcortical structures (such as the medial diencephalon and pontomesencephalic reticular formation), leading secondarily to widespread inhibition of nonseizing cortical regions, which may in turn be responsible for behavioral manifestations such as loss of consciousness during complex partial seizures.     

Noninvasive transcranial direct current stimulation in a genetic absence model

The proposed area of onset for absence epilepsy characteristic of spontaneously occurring spike and slow-wave discharges (SWDs) in the genetic absence rat model is the subgranular layer of the somatosensory cortex. Modulation of the hyperexcitable cortical foci by bilateral transcranial direct current stimulation (tDCS) might change the expression of SWDs. The effects of cathodal and anodal tDCS as well as cumulative effects of different intensities of repeated cathodal stimulation on EEG and behavior were examined. Cathodal tDCS reduced the number of SWDs during stimulation and affected the mean duration after stimulation both in an intensity-dependent manner. Behavior was changed after the highest stimulation intensity. Spectral analyses of the EEG during stimulation revealed an increase in sub-delta and delta frequency ranges, suggesting that cortical cells were hyperpolarized. Cathodal tDCS might be an effective non-invasive tool to decrease cortical excitability, presumably in focal zone in this genetic model.     

Corticothalamic modulation during absence seizures in rats: a functional MRI assessment

PURPOSE: Functional magnetic resonance imaging (fMRI) was used to identify areas of brain activation during absence seizures in an awake animal model. METHODS: Blood-oxygenation-level-dependent (BOLD) fMRI in the brain was measured by using T2*-weighted echo planar imaging at 4.7 Tesla. BOLD imaging was performed before, during, and after absence seizure induction by using gamma-butyrolactone (GBL; 200 mg/kg, intraperitoneal). RESULTS: The corticothalamic circuitry, critical for spike-wave discharge (SWD) formation in absence seizure, showed robust BOLD signal changes after GBL administration, consistent with EEG recordings in the same animals. Predominantly positive BOLD changes occurred in the thalamus. Sensory and parietal cortices showed mixed positive and negative BOLD changes, whereas temporal and motor cortices showed only negative BOLD changes. CONCLUSIONS: With the BOLD fMRI technique, we demonstrated signal changes in brain areas that have been shown, with electrophysiology experiments, to be important for generating and maintaining the SWDs that characterize absence seizures. These results corroborate previous findings from lesion and electrophysiological experiments and show the technical feasibility of noninvasively imaging absence seizures in fully conscious rodents.