Electroencephalography Electrodes Research Articles

Characteristics of seizures onset discharges and surgical outcome in patients with mesial temporal lobe epilepsy

Objective To explore the seizure originating pattern, high-frequency activity and surgical outcome of mesial temporal lobe epilepsy. Methods A total of 12 patients with intractable epilepsy were retrospectively enrolled in this study, who were admitted to Epilepsy Center of Yuquan Hospital, Tsinghua University, and underwent mesial temporal lobectomy from January 2014 to December 2015. Stereotactic electroencephalography (SEEG) electrodes were implanted and the diagnosis of mesial temporal lobe was confirmed. All patients were divided into hypersynchronous (HYP) group and low voltage fast (LVF) group based on the seizure onset pattern on SEEG. Selective amygdalohippocampectomy (SAH) was performed in 11 cases and standard anterior temporal lobectomy (ATL) in 1 case. Postoperative follow-up was performed and surgical outcomes were evaluated according to the Engel scale. Results A total of 139 electrodes were implanted in 12 patients with an average of (11.6±0.7) electrodes in each, which had 1 705 contacts with an average of (142.1±9.8) contacts in each case. In total, 60 seizures were recorded, among which seizures started as HYP in 7 cases, LVF in 4 cases and poly spikes in 1 case. Compared with HYP group, LVF involved more contacts (23 vs.28, P<0.05) and propagated faster (11.2±2.3 s vs. 7.1±1.0 s, P<0.05). High frequency oscillation existed before both HYP and LVF occurred. Postsurgical follow-up lasted 12~24 months with an average of (14.7±3.5)months. All patients in HYP group became seizure free and were classified as Engel Ⅰ. In LVF group, 1 case reported 2 severe attacks in total and 2~3 mild attacks per month; and 1 case had 1~2 severe attacks per month, and both were classified as Engel Ⅲ. Postoperative outcome in HYP group was better than that in LVF group (χ2=4.278, P<0.05). Conclusions The discharge patterns of seizure onset in mesial temporal lobe epilepsy include HYP and LVF. Patients with HYP as seizure onset pattern seemed to have better surgical outcomes. High frequency activity might start prior to HYP and LVF and serve as electrophysiological evidence and clinical assistance. Key words: Epilepsy, temporal lobe; Stereoelectroencephalography; Hypersynchronous; Low voltage fast; High frequency oscillation; Treatment outcome

State‐Dependent Expiratory Abdominal Activity During Hypercapnia in Adult Unanaesthetized Rats

Expiration at rest is a passive process. Expiratory muscles (ex: abdominals) are recruited in situations where respiratory demand is increased, such as during hypercapnia, leading to emergence of active expiration (A.E.). The present study tested: (i) the hypothesis that A.E. occurs in a state‐dependent manner (sleep‐wake cycle) during hypercapnia exposure in adult rats and (ii) the functional effects of A.E. in the pulmonary ventilation (VE). Wistar rats (280–330g) were implanted with electrodes for electroencephalography (EEG) and electromyography (EMG) of the neck, diaphragm (DIA) and abdominal (ABD) muscles. A.E. events were considered as rhythmic contraction of the abdominal muscle interposed to diaphragm (i.e., the expiration period). VE was measured by the barometric method. At least eight days after surgery, animals were submitted to the experimental protocol. Animals were allowed to acclimate in the chamber (~30 min). After this period, EEG and EMG wires were connected and animals were exposed (~60 min) to room air and hypercapnia (7% CO2). EEG, EMG and VE were recorded. The results demonstrate that regardless of state, there was no A.E. during room air. During hypercapnia, A.E. occurred in both states, wakefulness and sleep. The DIA‐to‐ABD ratio indicated that the occurrence of A.E. was predominant during non‐REM sleep. When A.E. was present, the VE had a positive correlation (p&lt;0.05) with peak amplitude of ABDEMG activity. The higher the amplitude of ABDEMG, the higher was VE values. Furthermore, in both wakefulness and sleep, VE was also higher (p&lt;0.05) in periods with A.E. compared to periods in which there were no A.E. events These data indicate the predominant expression of A.E. during sleep and its functional role to support VE in conditions of increased respiratory demand.Support or Funding InformationSao Paulo Research Foundation (FAPESP #2013/17606‐9)

Paradoxical Emergence: Administration of Subanesthetic Ketamine during Isoflurane Anesthesia Induces Burst Suppression but Accelerates Recovery.

Promoting arousal by manipulating certain brain regions and/or neurotransmitters has been a recent research focus, with the goal of trying to improve recovery from general anesthesia. The current study tested the hypothesis that a single subanesthetic dose of ketamine during isoflurane anesthesia would increase cholinergic tone in the prefrontal cortex and accelerate recovery. Adult male rats were implanted with electroencephalography electrodes (frontal, parietal, and occipital cortex) and a microdialysis guide cannula targeted for the prefrontal cortex. After establishing general anesthesia with isoflurane, animals were randomly assigned to receive a saline control or ketamine injection. When isoflurane was discontinued nearly 90 min after drug or saline administration, recovery from anesthesia was measured by experimenters and blinded observers. During the entire experiment, electrophysiologic signals were recorded and acetylcholine was quantified by high-performance liquid chromatography with electrochemical detection. A single dose of subanesthetic ketamine caused an initial 125% increase in burst suppression ratio (last isoflurane sample: 37.48 ± 24.11% vs. isoflurane after ketamine injection: 84.36 ± 8.95%; P < 0.0001), but also a significant 44% reduction in emergence time (saline: 877 ± 335 s vs. ketamine: 494 ± 108 s; P = 0.0005; n = 10 per treatment). Furthermore, ketamine caused a significant 317% increase in cortical acetylcholine release (mean after ketamine injection: 0.18 ± 0.16 pmol vs. ketamine recovery: 0.75 ± 0.41 pmol; P = 0.0002) after isoflurane anesthesia was discontinued. Administration of subanesthetic doses of ketamine during isoflurane anesthesia increases anesthetic depth but-paradoxically-accelerates the recovery of consciousness, possibly through cholinergic mechanisms.

Electroencephalographic electrode montage in goats: topographical, radiological, and physiological assessment

Electroencephalographic electrode montage in goats: topographical, radiological, and physiological assessment

A Single‐Trial Multiclass Classification of Various Motor Imagery Tasks for EEG‐Based Brain–Computer Interface Communication

SUMMARYWe studied the brain activity (alpha and beta rhythms) with various motor imagery tasks for improvement of brain–computer interface (BCI) usability using 14 electroencephalography (EEG) electrodes in five healthy subjects. For this purpose, we estimated two‐class and four‐class classification accuracy on the EEG signals with four motor imagery tasks derived from each type motor imagery (three classical motor imagery and one proposed mental strategy) task using t‐test and super vector machine. The proposed mental strategy was imagery writing Kanji (Japanese characters). It has the possibility of both sensorimotor cortex and the visual cortex activation. Therefore, we expected to extract the distinct activity different from the activation with classical motor imagery tasks. In the two‐class classification results, the classification accuracy was 73.7% on average in all combination of derived motor imagery task. Moreover, we demonstrated that four‐class classification accuracy was 40.1% and the proposed task had possibility of the visual cortex activation dominantly. In experimental results, we proposed the new way for improvement of BCI application usability.

New Flexible Silicone-Based EEG Dry Sensor Material Compositions Exhibiting Improvements in Lifespan, Conductivity, and Reliability.

This study investigates alternative material compositions for flexible silicone-based dry electroencephalography (EEG) electrodes to improve the performance lifespan while maintaining high-fidelity transmission of EEG signals. Electrode materials were fabricated with varying concentrations of silver-coated silica and silver flakes to evaluate their electrical, mechanical, and EEG transmission performance. Scanning electron microscope (SEM) analysis of the initial electrode development identified some weak points in the sensors’ construction, including particle pull-out and ablation of the silver coating on the silica filler. The newly-developed sensor materials achieved significant improvement in EEG measurements while maintaining the advantages of previous silicone-based electrodes, including flexibility and non-toxicity. The experimental results indicated that the proposed electrodes maintained suitable performance even after exposure to temperature fluctuations, 85% relative humidity, and enhanced corrosion conditions demonstrating improvements in the environmental stability. Fabricated flat (forehead) and acicular (hairy sites) electrodes composed of the optimum identified formulation exhibited low impedance and reliable EEG measurement; some initial human experiments demonstrate the feasibility of using these silicone-based electrodes for typical lab data collection applications.

Incorporating modern neuroscience findings to improve brain–computer interfaces: tracking auditory attention

Objective. Brain–computer interface (BCI) technology allows users to generate actions based solely on their brain signals. However, current non-invasive BCIs generally classify brain activity recorded from surface electroencephalography (EEG) electrodes, which can hinder the application of findings from modern neuroscience research. Approach. In this study, we use source imaging—a neuroimaging technique that projects EEG signals onto the surface of the brain—in a BCI classification framework. This allowed us to incorporate prior research from functional neuroimaging to target activity from a cortical region involved in auditory attention. Main results. Classifiers trained to detect attention switches performed better with source imaging projections than with EEG sensor signals. Within source imaging, including subject-specific anatomical MRI information (instead of using a generic head model) further improved classification performance. This source-based strategy also reduced accuracy variability across three dimensionality reduction techniques—a major design choice in most BCIs. Significance. Our work shows that source imaging provides clear quantitative and qualitative advantages to BCIs and highlights the value of incorporating modern neuroscience knowledge and methods into BCI systems.

Dynamics of sensorimotor cortex activation during absence and myoclonic seizures in a mouse model of juvenile myoclonic epilepsy.

Generalized epilepsy syndromes often confer multiple types of seizures, but it is not known if these seizures activate separate or overlapping brain networks. Recently, we reported that mice with a juvenile myoclonic epilepsy mutation (Gabra1[A322D]) exhibited both absence and myoclonic generalized seizures. Here, we determined the time course of sensorimotor cortex activation and the spatial distribution of spike voltage during these two seizures. We implanted Gabra1+/A322D mice with multiple electroencephalography (EEG) electrodes over bilateral somatosensory cortex barrel fields (S1) and anterior (aM1) and posterior (pM1) motor cortices and recorded absence seizures/spike-wave discharges (SWDs) and myoclonic seizures. We used nonlinear-association analyses and cross-correlation calculations to determine the strength, leading regions, and time delays of cortical coupling from the preictal to ictal states and within the spike and interspike periods. The distribution of spike voltage was also measured in SWDs and myoclonic seizures. EEG connectivity among all electrode pairs increased at the onset of both SWDs and myoclonic seizures. Surprisingly, during spikes of both seizure types, S1 led M1 with similar delay times. Myoclonic seizure spikes started more focally than SWD spikes, with a significant majority appearing first only in S1 electrodes, whereas a substantial fraction of SWD spikes were detected first in S1 and at least one M1 electrode. The absolute voltage of myoclonic seizure spikes was significantly higher than that of SWD spikes, and there was a greater relative voltage over M1 during myoclonic seizure spikes than in the first one to two SWD spikes. The leading sites in S1 and similar delay times suggest both SWDs and myoclonic seizures activate overlapping networks in sensorimotor cortex and thus, therapeutically targeting of this network could potentially treat both seizures. Spike focality, absolute voltage, and voltage distribution provide insight into neuronal activation during these two seizure types.

Cost-utility analysis of magnetoencephalography used to inform intracranial electrode placement in patients with drug resistant epilepsy: a model based analysis.

We estimated the cost-effectiveness of adding magnetoencephalography to a standard assessment for epilepsy surgery consisting of neuropsychology, magnetic resonance imagining, scalp electroencephalography, video electroencephalography and intracranial electroencephalography, in the capacity of informing intracranial electroencephalography electrode placement. We used Microsoft Excel (2007) to construct a decision model. Discounted costs and quality adjusted life years are aggregated to calculate incremental cost-effectiveness ratios. Sensitivity analyses are conducted to assess robustness of findings. Our base case analysis yielded a result of $14 300 per quality adjusted life year gained. A total of 82.7% of probabilistic sensitivity analysis iterations resulted in incremental cost-effectiveness ratios below $100 000 in 2014 Canadian dollars. Our findings demonstrate that the inclusion of Magnetoencephalography in the assessment for epilepsy surgery in the capacity of informing intracranial electroencephalography electrode placement is likely not cost saving but does represent a reasonable allocation of resources from a value for money perspective.

Polymer-based candle-shaped microneedle electrodes for electroencephalography on hairy skin

In this paper, we report on the optimization of the shape of dry microneedle electrodes for electroencephalography (EEG) on hairy locations and compare the electrodes we developed with conventional wet electrodes. We propose the use of SU-8-based candle-shaped microneedle electrodes (CMEs), which have pillars of 1.0 mm height and 0.4 mm diameter with a gap of 0.43 mm between pillars. Microneedles are formed on the top of the pillars. The shape was determined by how well the pillars can avoid hairs and support the microneedles to penetrate through the stratum corneum. The skin–electrode contact impedances of the fabricated CMEs were found to be higher and less stable than those of conventional wet electrodes. However, the CMEs successfully acquired signals with qualities as good as those of conventional wet electrodes. Given the usability of the CMEs, which do not require skin preparation or gel, they are promising alternatives to conventional wet electrodes.

Electrophysiological alterations in a complex rat model of schizophrenia

BackgroundPsychiatric disorders are frequently accompanied by changes in brain electrical oscillations and abnormal auditory event related potentials. The goal of this study was to characterize these parameters of a new rat substrain showing several alterations related to schizophrenia. MethodsMale rats of the new substrain, developed by selective breeding after combined subchronic ketamine treatment and postweaning social isolation, and naive Wistar ones group-housed without any interventions were involved in the present study. At the age of 3 months, animals were implanted with cortical electroencephalography electrodes. Auditory evoked potentials during paired-click stimuli and power of oscillation in different frequency bands were determined with and without acute ketamine (20mg/kg) treatment. ResultsRegarding the auditory evoked potentials, the latency of P2 was delayed and the amplitude of N1 peak was lower in the new substrain. The new substrain showed increased power of oscillations in the theta, alpha and beta bands, while decreased power was detected in delta and gamma2 bands (52–70Hz) compared with control animals. Acute ketamine treatment increased the gamma1 band (30–48Hz) power in both groups, while it elicited significant changes only in the new substrain in the total power and in alpha, beta and gamma2 bands. ConclusionsThe validation of the translational utility of this new rat substrain by electrophysiological investigations revealed that these rats show abnormalities that may model a part of the neurophysiological deficits observed in schizophrenia.

Clinical symptom analysis of hypermotor seizures originated from the insular-opercular epilepsy

Objective To investigate the value of the characteristics of hypermotor seizures in the localization of epileptogenic zone by studying the clinical symptom characteristics originated from the insular-opercular epilepsy. Methods From June 2006 to March 2014, the clinical data of 5 patients with intractable epilepsy of hypermotor seizures including history, imaging, scalp electroencephalogram, and intracranial electrode electroencephalography admitted to the Department of Neurosurgery, Tsinghua University Yuquan Hospital were studied retrospectively. Results In 5 patients, there was 1 with hypermotor seizures type Ⅰ, 2 with hypermotor type Ⅱ, and 2 with mixed type. Three patients accompanied with bilateral asymmetric rigidity. They were located in the contralateral epileptic foci. Five patients had an aura before seizures, 2 of them had a somatosensory aura on the contralateral side, 1 had palpitations, and 2 had a non-specific aura. The seizures of 2 patients originated from the left hemisphere and 3 from the right hemisphere. Four patients had brain area discharge in the intermittent period. They were located on the ipsilateral epileptic zones. No epileptiform discharges were observed in 1 case. Two patients had generalized ictal onset on the ictal electroencephalogram, the other 3 had unilateral hemisphere or unilateral ictal onset. Conclusions Seizures initiated from insular-opercular cortex can show any type in hypermotor seizures. The asymmetric rigidity of specific aura before onset and in hypermotor seizures has the lateralization value. The special facial expression in seizers is more common in hypermotor seizures originated from the insular-opercular cortex. Key words: Epilepsy; Hypermotor seizures; Insular-opercular; Electroencephalography

Development of a Brain-Computer Interface Based on Visual Stimuli for the Movement of a Robot Joints

This paper presents a brain computer interface (BCI) to control a robotic arm by brain signals from visual stimuli. The following signal processing steps were established; acquisition of brain signals by electroencephalography (EEG) electrodes; noise reduction; extraction of signal characteristics and signal classification. Reliable brain signals were obtained by the use of the Emotiv EPOC® commercial hardware. The OpenViBE® commercial software was used to program the signal processing algorithms. By using Matlab® together with an Arduino® electronic board, two servo motors were controlled to drive two joints of a 5 degrees-of-freedom robot commanded by P300-type evoked potential brain signals from visual stimulation when a subject concentrates on particular images from an image matrix displayed in the computer screen. The experiments were conducted with and without auditive and visual noise (artifacts) to find out the noise influence in the signal classification outcome. The obtained experimental results presented an efficiency in the identification stage up to 100% with and without hearing noise conditions. However, under visual noise conditions a maximum efficiency of 50% was reached. The experiments for the servomotors control were carried out without noise, reaching an efficiency of 100% in the identification stage.

Learning intervention-induced deformations for non-rigid MR-CT registration and electrode localization in epilepsy patients.

This paper describes a framework for learning a statistical model of non-rigid deformations induced by interventional procedures. We make use of this learned model to perform constrained non-rigid registration of pre-procedural and post-procedural imaging. We demonstrate results applying this framework to non-rigidly register post-surgical computed tomography (CT) brain images to pre-surgical magnetic resonance images (MRIs) of epilepsy patients who had intra-cranial electroencephalography electrodes surgically implanted. Deformations caused by this surgical procedure, imaging artifacts caused by the electrodes, and the use of multi-modal imaging data make non-rigid registration challenging. Our results show that the use of our proposed framework to constrain the non-rigid registration process results in significantly improved and more robust registration performance compared to using standard rigid and non-rigid registration methods.

Electroencephalographic markers of robot-aided therapy in stroke patients for the evaluation of upper limb rehabilitation.

Stroke is the leading cause of permanent disability in developed countries; its effects may include sensory, motor, and cognitive impairment as well as a reduced ability to perform self-care and participate in social and community activities. A number of studies have shown that the use of robotic systems in upper limb motor rehabilitation programs provides safe and intensive treatment to patients with motor impairments because of a neurological injury. Furthermore, robot-aided therapy was shown to be well accepted and tolerated by all patients; however, it is not known whether a specific robot-aided rehabilitation can induce beneficial cortical plasticity in stroke patients. Here, we present a procedure to study neural underpinning of robot-aided upper limb rehabilitation in stroke patients. Neurophysiological recordings use the following: (a) 10-20 system electroencephalographic (EEG) electrode montage; (b) bipolar vertical and horizontal electrooculographies; and (c) bipolar electromyography from the operating upper limb. Behavior monitoring includes the following: (a) clinical data and (b) kinematic and dynamic of the operant upper limb movements. Experimental conditions include the following: (a) resting state eyes closed and eyes open, and (b) robotic rehabilitation task (maximum 80 s each block to reach 4-min EEG data; interblock pause of 1 min). The data collection is performed before and after a program of 30 daily rehabilitation sessions. EEG markers include the following: (a) EEG power density in the eyes-closed condition; (b) reactivity of EEG power density to eyes opening; and (c) reactivity of EEG power density to robotic rehabilitation task. The above procedure was tested on a subacute patient (29 poststroke days) and on a chronic patient (21 poststroke months). After the rehabilitation program, we observed (a) improved clinical condition; (b) improved performance during the robotic task; (c) reduced delta rhythms (1-4 Hz) and increased alpha rhythms (8-12 Hz) during the resting state eyes-closed condition; (d) increased alpha desynchronization to eyes opening; and (e) decreased alpha desynchronization during the robotic rehabilitation task. We conclude that the present procedure is suitable for evaluation of the neural underpinning of robot-aided upper limb rehabilitation.

Design Principles and Dynamic Front End Reconfiguration for Low Noise EEG Acquisition With Finger Based Dry Electrodes.

Dry electrodes are a convenient alternative to wet electrodes for electroencephalography (EEG) acquisition systems. Dry electrodes are subject to a higher amount of noise at the electrode scalp interface and these effects can be worsened due to non-ideal design or improper placement on the head. In this work, we investigate a popular dry electrode design based on a number of resistive 'finger' shaped contacts. We conduct experiments comparing designs with varying numbers of fingers using two impedance measurement methods and show that sparser arrangements of fingers are more robust to varying use cases and are more effective at penetrating through hair on the scalp. We then show that these impedance measurement metrics could be used to sort individual fingers within one electrode according to quality of electrical contact. We show that the signals from individual fingers can differ from each other significantly due to differing local effects of impedance and noise, and demonstrate through experimental results that dynamically selecting only a subset of fingers with good contact impedance can improve the overall signal-to-noise ratio of the EEG signal from that electrode.

Self-Adhesive and Capacitive Carbon Nanotube-Based Electrode to Record Electroencephalograph Signals From the Hairy Scalp.

We fabricated a carbon nanotube (CNT)/adhesive polydimethylsiloxane (aPDMS) composite-based dry electroencephalograph (EEG) electrode for capacitive measuring of EEG signals. As research related to brain-computer interface applications has advanced, the presence of hairs on a patient's scalp has continued to present an obstacle to recorder EEG signals using dry electrodes. The CNT/aPDMS electrode developed here is elastic, highly conductive, self-adhesive, and capable of making conformal contact with and attaching to a hairy scalp. Onto the conductive disk, hundreds of conductive pillars coated with Parylene C insulation layer were fabricated. A CNT/aPDMS layer was attached on the disk to transmit biosignals to the pillar. The top of disk was designed to be solderable, which enables the electrode to connect with a variety of commercial EEG acquisition systems. The mechanical and electrical characteristics of the electrode were tested, and the performances of the electrodes were evaluated by recording EEGs, including alpha rhythms, auditory-evoked potentials, and steady-state visually-evoked potentials. The results revealed that the electrode provided a high signal-to-noise ratio with good tolerance for motion. Almost no leakage current was observed. Although preamplifiers with ultrahigh input impedance have been essential for previous capacitive electrodes, the EEGs were recorded here by directly connecting a commercially available EEG acquisition system to the electrode to yield high-quality signals comparable to those obtained using conventional wet electrodes.

Multimodal 2D Brain Computer Interface.

In this work we used multimodal, non-invasive brain signal recording systems, namely Near Infrared Spectroscopy (NIRS), disc electrode electroencephalography (EEG) and tripolar concentric ring electrodes (TCRE) electroencephalography (tEEG). 7 healthy subjects participated in our experiments to control a 2-D Brain Computer Interface (BCI). Four motor imagery task were performed, imagery motion of the left hand, the right hand, both hands and both feet. The signal slope (SS) of the change in oxygenated hemoglobin concentration measured by NIRS was used for feature extraction while the power spectrum density (PSD) of both EEG and tEEG in the frequency band 8-30Hz was used for feature extraction. Linear Discriminant Analysis (LDA) was used to classify different combinations of the aforementioned features. The highest classification accuracy (85.2%) was achieved by using features from all the three brain signals recording modules. The improvement in classification accuracy was highly significant (p = 0.0033) when using the multimodal signals features as compared to pure EEG features.

Limitations of functional magnetic resonance imaging in mapping function near a vascular lesion: A case study

We present a case of functional reorganization of the somatosensory system in a 15 year-old female with a history of perinatal stroke of the middle cerebral artery. The patient presented with hemiparesis and epilepsy and underwent comprehensive pre-surgical evaluation for epilepsy surgery, including mapping of somatosensory function with functional magnetic resonance imaging (fMRI). The fMRI results indicated inter-hemispheric reorganization of somatosensory function from the left to the right hemisphere, and showed no residual somatosensory function in the peri-lesional area of the affected left hemisphere. However, following implantation of subdural electroencephalography (EEG) electrodes, recordings from left hemisphere lesional and peri-lesional areas showed evoked electrophysiological responses to tactile stimulation. Bedside and intra-operative stimulation mapping confirmed multiple somatosensory responsive sites in the left hemisphere in or near the lesion, in contradiction of the fMRI results. Since the BOLD signal is a measure of the local ratio of oxygenated to deoxygenated blood, fMRI represents only an indirect measure of neuronal activity. Modeling of fMRI activation depends on intact neurovascular coupling and adequate signal to noise ratios, which may be altered in the presence of a vascular lesion. Our results suggest that pre-surgical mapping of cortical function with fMRI can be unreliable in the presence of a vascular lesion and can lead to false-negative results. In such cases, direct measures of electrophysiological activity, such as electrocorticography, scalp EEG and MEG should be preferred.

Anti-absence activity of mGlu1 and mGlu5 receptor enhancers and their interaction with a GABA reuptake inhibitor: Effect of local infusions in the somatosensory cortex and thalamus.

Glutamate and γ-aminobutyric acid (GABA) are the key neurotransmitter systems in the cortical-thalamocortical network, involved in normal and pathologic oscillations such as spike-wave discharges (SWDs), which characterize different forms of absence epilepsy. Metabotropic glutamate (mGlu) and GABA receptors are widely expressed within this network. Herein, we examined the effects of two selective positive allosteric modulators (PAMs) of mGlu1 and mGlu5 receptors, the GABA reuptake inhibitor, tiagabine, and their interaction in the somatosensory cortex and thalamus on SWDs in WAG/Rij rats. Male WAG/Rij rats were equipped with bilateral cannulas in the somatosensory cortex (S1po) or the ventrobasal (VB) thalamic nuclei, and with cortical electroencephalography (EEG) electrodes. Rats received a single dose of the mGlu1 receptor PAM, RO0711401, or the mGlu5 receptor PAM, VU0360172, various doses of tiagabine, or VU0360172 combined with tiagabine. Both PAMs suppressed SWDs regardless of the site of injection. Tiagabine enhanced SWDs when injected into the thalamus, but, unexpectedly, suppressed SWDs in a dose-dependent manner when injected into the cortex. Intracortical co-injection of VU0360172 and tiagabine produced slightly larger effects as compared to either VU0360172 or tiagabine alone. Intrathalamic co-injections of VU0360172 and subthreshold doses of tiagabine caused an antiabsence effect similar to that exhibited by VU0360172 alone in the first 10 min. At 30 min, however, the antiabsence effect of VU0360172 was prevented by subthreshold doses of tiagabine, and the combination produced a paradoxical proabsence effect at 40 and 50 min. These data (1) show that mGlu1 and mGlu5 receptor PAMs reduce absence seizures acting at both thalamic and cortical levels; (2) demonstrate for the first time that tiagabine, despite its established absence-enhancing effect, reduces SWDs when injected into the somatosensory cortex; and (3) indicate that the efficacy of VU0360172 in the thalamus may be critically affected by the availability of (extra)synaptic GABA.