De novo status epilepticus possibly related to battery depletion of anterior thalamic brain stimulator.

Anterior thalamic deep brain stimulation is an effective therapeutic option for patients with drug-refractory focal epilepsy who are poor surgical candidates. Although the precise mechanism of action of thalamic neurostimulation is unknown, studies demonstrating increased efficacy over time have raised the possibility that therapeutic benefits are mediated by stimulation-related long-term neuroplastic changes. Adverse effects related to hardware malfunction have been previously described, and most commonly include local infection, sensory disturbances, and migration of leads. However, the withdrawal effect of sudden deep brain stimulation malfunction on seizure control is unclear. We present the case of a 21-year-old patient with intractable focal epilepsy who developed status epilepticus concurrently with unexpected deep brain stimulator battery failure, 21 months post implantation. This case demonstrates an unfamiliar possible adverse effect of anterior thalamic stimulation withdrawal and emphasizes the importance of stimulator hardware assessment in patients presenting with seizure worsening.

Deep brain stimulation in patients with long history of drug resistant epilepsy and poor functional status: Outcomes based on the different targets.

BACKGROUND: Deep brain stimulation (DBS) is a widely used surgical procedure for the treatment of patients with drug resistant epilepsy (DRE) and several anatomical target have been described. Indications for DBS includes patients with focal, partial seizure and those for which resective or disconnective surgery are contraindicated, such as involvement of eloquent cortex or significant comorbidities. Despite the SANTE trial has clearly indicated the efficacy of DBS of anterior nucleus of the thalamus (ANT), specific indications regarding the best anatomical target and outcome in patients with severe disability are lacking. Here we described our case series of patients underwent DBS of three different target including ANT, centromedian thalamic nucleus (CMN) and subthalamic nucleus (STN). METHOD: Six patients with DRE have been treated with DBS of ANT (n = 3), STN (n = 2) and CMN (n = 1). Outcome has been expressed as seizures frequency reduction and patients functional status after surgery with a follow-up of 5-11 years. RESULTS: Four out of six patients show no reduction of seizures frequency after DBS implant with one case of increasing atypical absence. Two cases, one ANT and one CMN, show a significant reduction of seizures frequency of 50-60%. No patients improve relative to functional outcome and one showed psychiatric symptoms worsening. CONCLUSIONS: For patients with DRE and severe functional disability, DBS may reduce seizure frequency in some cases, but it does not improve functional outcome.

Anterior thalamic dysfunction underlies cognitive deficits in a subset of neuropsychiatric disease models.

Neuropsychiatric disorders are often accompanied by cognitive impairments/intellectual disability (ID). It is not clear whether there are converging mechanisms underlying these debilitating impairments. We found that many autism and schizophrenia risk genes are expressed in the anterodorsal subdivision (AD) of anterior thalamic nuclei, which has reciprocal connectivity with learning and memory structures. CRISPR-Cas9 knockdown of multiple risk genes selectively in AD thalamus led to memory deficits. While the AD is necessary for contextual memory encoding, the neighboring anteroventral subdivision (AV) regulates memory specificity. These distinct functions of AD and AV are mediated through their projections to retrosplenial cortex, using differential mechanisms. Furthermore, knockdown of autism and schizophrenia risk genes PTCHD1, YWHAG, or HERC1 from AD led to neuronal hyperexcitability, and normalization of hyperexcitability rescued memory deficits in these models. This study identifies converging cellular to circuit mechanisms underlying cognitive deficits in a subset of neuropsychiatric disease models.

Thalamic oscillatory activity may predict response to deep brain stimulation of the anterior nuclei of the thalamus.

We hypothesized that local/regional properties of stimulated structure/circuitry contribute to the effect of deep brain stimulation (DBS). We analyzed intracerebral electroencephalographic (EEG) recordings from externalized DBS electrodes targeted bilaterally in the anterior nuclei of the thalamus (ANT) in 12 patients (six responders, six nonresponders) with more than 1 year of follow-up care. In the bipolar local field potentials of the EEG, spectral power (PW) and power spectral entropy (PSE) were calculated in the passbands 1-4, 4-8, 8-12, 12-20, 20-45, 65-80, 80-200 and 200-500 Hz. The most significant differences between responders and nonresponders were observed in the BRIDGE area (bipolar recordings with one contact within the ANT and the second contact in adjacent tissue). In responders, PW was significantly decreased in the frequency bands of 65-80, 80-200, and 200-500 Hz (p < .05); PSE was significantly increased in all frequency bands (p < .05) except for 200-500 Hz (p = .06). The local EEG characteristics of ANT recorded after implantation may play a significant role in DBS response prediction.

Precision mapping of the epileptogenic network with low- and high-frequency stimulation of anterior nucleus of thalamus.

OBJECTIVE: The goal of thalamic deep brain stimulation in epilepsy is to engage and modulate the epileptogenic network. We demonstrate how the anterior nucleus of thalamus (ANT) stimulation engages the epileptogenic network using electrophysiological measures (gamma response and post-stimulation excitability). METHODS: Five patients with suspected temporal lobe epilepsy syndrome, undergoing stereo-electroencephalography (SEEG), were enrolled in the IRB approved study to undergo recording and stimulation of the ANT. We analyzed the extent of gamma-band response (activation or suppression) and post-stimulation change in excitability in various cortical regions during low (10 Hz) and high (50 Hz) frequency stimulations. RESULTS: 10 Hz stimulation increased cortical gamma, whereas 50 Hz stimulation suppressed the gamma responses. The maximum response to stimuli was in the hippocampus. High epileptogenicity regions were more susceptible to stimulation. Both 10-and 50 Hz stimulations decreased post-stimulation cortical excitability. The greater the gamma-band activation with 10 Hz stimulation, the greater was the decrease in post-stimulation excitability. CONCLUSIONS: We define an EEG marker that delineates stimulation-specific nodal engagement. We proved that nodes that were engaged with the thalamus during stimulation were more likely to show a short term decrease in post-stimulation excitability. SIGNIFICANCE: Patient-specific engagement patterns during stimulation can be mapped with SEEG that can be used to optimize stimulation parameters.

Headache Perception in an Epilepsy Patient with Neuromodulation by Anterior Thalamic Nuclei Deep Brain Stimulation: A Case Report.

OBJECTIVE: Headache disorders are frequently associated with epilepsy. Some neuromodulation techniques for refractory epilepsy have been reported to positively influence the associated chronic headache. However, the exact mechanism of action of vagus nerve stimulation (VNS) and anterior thalamic nuclei-deep brain stimulation (ANT-DBS) on pain perception is unclear. METHOD: We report a structured assessment of pain perception in a patient who experienced headache relief after ANT-DBS for refractory focal epilepsy and compare it with pain perception of epilepsy patients with chronic headache who were treated with and without VNS. RESULTS: The pain-associated symptoms in the ANT-DBS case were on the Pain Anxiety Symptoms Scale (PASS-40) subscore "physiological anxiety" closer to the control collective, whereas in patients with VNS, this was more likely for the PASS-40 subscores "cognitive anxiety" or "escape and avoidance." CONCLUSION: ANT-DBS and VNS may influence epilepsy-associated chronic headache in different ways.

Probing circuit of Papez with stimulation of anterior nucleus of the thalamus and hippocampal evoked potentials.

PURPOSE: Despite documented clinical effectiveness, deep brain stimulation (DBS) therapy for drug-resistant epilepsy rarely yields long-term seizure free outcomes. METHODS: This pilot study in five patients investigated circuit of Papez evoked potentials (EPs) using hippocampal sensing during anterior nucleus of the thalamus (ANT) electrical stimulation. We hypothesize that hippocampal EP is a potential biomarker that could be useful for ANT electrode targeting and improving seizure reduction. We obtained bilateral circuit of Papez EPs in five patients with bilateral temporal lobe epilepsy (TLE). The circuit of Papez EPs were measured and assessed by signal amplitude. Volumetric analysis of relevant mesial temporal structures and ANT stimulation analysis was performed on immediate post-implantation images. RESULTS: The patient with the most favorable seizure outcome, which meant long-term seizure reduction greater than 50 % compared to baseline, had strong bilateral EPs and normal hippocampal structure. Conversely, those without clinical benefit with ANT DBS had absent or weak bilateral EPs as well as MRI findings consistent with mesial temporal sclerosis (MTS). CONCLUSION: The data support the hypothesis that hippocampal EPs with ANT stimulation may be used to as a surrogate marker to probe circuit of Papez and predict ANT DBS efficacy.

Effects of anterior thalamic nuclei stimulation on gene expression in a rat model of temporal lobe epilepsy.

Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) has been shown to be effective and safe in the long-term treatment of refractory epilepsy. However, the mechanisms by which ANT-DBS controls epilepsy at the gene expression level (e.g., which regulatory mechanisms are altered) is not well understood. Nine rats were randomly assigned to the control group, the kainic acid (KA) group, and the DBS group. Temporal lobe epilepsy in rats was induced by a stereotaxic KA injection (KA group). The DBS group received the KA injection followed by treatment with ANT-DBS. Video-electroencephalogram (EEG) was used to monitor seizures. Total RNA samples were isolated from the hippocampus of three groups. Microarray was used to detect differentially regulated mRNAs. GO and pathway analysis were performed to analyze the functional categories and affected pathways. qPCR was used to prove the reliability of the microarray results. The differentially expressed genes the KA group and the DBS group, relative to the control group, were screened and a total of 2910 genes were identified. These genes were involved in functional categories such as ion channel activity (P = 5.01 × 10-8), gated channel activity (P = 1.42 × 10-7), lipid binding (P = 4.97 × 10-5), and hydrolase activity (P = 5.02 × 10-5) and pathways such as calcium signaling pathway (P = 2.09 × 10-8), glutamatergic synapse (P = 4.09 × 10-8) and NOD-like receptor signaling pathway (P = 2.70 × 10-6). Differentially expressed mRNAs might play a role in the pathogenesis of temporal lobe epilepsy. Calcium signaling pathways, synaptic glutamate, and NOD-like receptor signaling pathway play a central role in normal-epilepsy-ANT-DBS treatment series. ANT-DBS achieves its antiepileptic effects by modulating target genes involved in a variety of functions and pathways.

Long-term outcome in neurostimulation of epilepsy.

For patients with pharmacoresistant focal epilepsy, neurostimulation offers nonpharmacological strategies to improve seizure control. Vagus nerve stimulation (VNS), deep brain stimulation of the anterior thalamic nuclei, and responsive neurostimulation (RNS) are approved therapies which have shown efficacy in randomized short-term trials. Controlled data from prospective studies are needed to confirm reports on stable or even increasing evidence from studies with longer follow-up and to confirm that neurostimulation may offer advantages also regarding cognitive tolerability and sudden unexpected death in epilepsy (SUDEP)-risk. Here, a review of long-term outcomes is given, highlighting both achievements in terms of efficacy and tolerability and limitations of conclusions thereon related to an uncontrolled data basis and decreasing cohort sizes. This article is part of the Special Issue? "Individualized Epilepsy Management: Medicines, Surgery and Beyond".

Do the rat anterior thalamic nuclei contribute to behavioural flexibility?

The rodent anterior thalamic nuclei (ATN) are vital for spatial memory. A consideration of their extensive frontal connections suggests that these nuclei may also subserve non-spatial functions. The current experiments explored the importance of the ATN for different aspects of behavioural flexibility, including their contribution to tasks typically associated with frontal cortex. In Experiment 1, rats with ATN lesions were tested on a series of response and visual discriminations in an operant box and, subsequently, in a water tank. The tasks included assessments of reversal learning as well switches between each discrimination dimension. Results revealed a mild and transient deficit on the operant task that was not specific to any stage of the procedure. In the water tank, the lesion animals were impaired on the reversal of a spatial discrimination but did not differ from controls on any other measure. Experiment 2 examined the impact of ATN damage on a rodent analogue of the 'Stroop', which assesses response choice during stimulus conflict. The lesion animals successfully acquired this task and were able to use contextual information to disambiguate conflicting cue information. However, responding during the initial presentation of conflicting cue information was affected by the lesion. Taken together, these results suggest that the ATN are not required for aspects of behavioural flexibility (discrimination learning, reversals or high-order switches) typically associated with the rat medial prefrontal cortex. The results from Experiment 2 suggest that the non-spatial functions of the ATN may be more aligned with those of the anterior cingulate cortex.

Electrical Stimulation of the Anterior Thalamus for Epilepsy: Clinical Outcome and Analysis of Efficient Target.

OBJECTIVE: Deep brain stimulation (DBS) of the anterior thalamic complex (ANT) is an adjunctive therapy for pharmacoresistant epilepsy. To define the most efficient target in DBS for epilepsy, we investigate clinical data, position of leads, usability of atlas data compared to electric field modeling based on programming parameters. METHODS: Data from ten consecutive patients who underwent ANT-DBS were analyzed. The mammillothalamic tract (MTT), an internal landmark for direct stereotactic targeting, was segmented from MRI. Centers of stimulation were determined and their positions relative to ventricles and the MTT were analyzed. Two 3D thalamus atlases were transformed to segmented patient's thalami and proportions of activated nuclei were calculated. RESULTS: Our data indicate higher response rates with a center of stimulation 5 mm lateral to the wall of the third ventricle (R2 for reduction of focal seizure frequency and distance to the wall of the third ventricle = 0.48, p = 0.026). For reduction of focal seizures, a strong positive correlation with the dorsal distance to the midcommissural plane was found (R2 = 0.66, p = 0.004). In one 3D atlas, stimulation of internal medullary lamina (IML) correlated strongly positive with response rates, which, however, did not reach statistical significance (R2 = 0.69, p = 0.17 for tonic-clonic seizures). All electrical fields covered the diameter of the MTT. The position of the MTT in the thalamus was highly variable (range: x-coordinate 4.0 to 7.3 mm, y-coordinate -1.3 to 5.1 mm in AC-PC space). CONCLUSIONS: The distance of the active contact to the lateral wall of the third ventricle, MTT and the ventrodorsal distance to midcommissural plane appear to be relevant for optimal target planning. For reduction of focal seizure frequency, we found best response rates with a center of stimulation 5 mm lateral to the wall of the third ventricle, and a lead tip 10 mm dorsal of the midcommissural plane.

Anterior thalamic nuclei, but not retrosplenial cortex, lesions abolish latent inhibition in rats.

The present study examined the effects of excitotoxic lesions in 2 closely related structures, the anterior thalamic nuclei and the retrosplenial cortex, on latent inhibition. Latent inhibition occurs when nonreinforced preexposure to a stimulus retards the subsequent acquisition of conditioned responding to that stimulus. Latent inhibition was assessed in a within-subject procedure with auditory stimuli and food reinforcement. As expected, sham-operated animals were slower to acquire conditioned responding to a stimulus that had previously been experienced without consequence, relative to a non-preexposed stimulus. This latent inhibition effect was absent in rats with excitotoxic lesions in the anterior thalamic nuclei, as these animals conditioned to both stimuli at equivalent rates. The retrosplenial lesions appeared to spare latent inhibition, as these animals displayed a robust stimulus preexposure effect. The demonstration here that anterior thalamic nuclei lesions abolish latent inhibition is consistent with emerging evidence of the importance of these thalamic nuclei for attentional control. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Automated detection of mesial temporal and temporoperisylvian seizures in the anterior thalamic nucleus.

BACKGROUND AND PURPOSE: Focal seizures can arise from coordinated activity across large-scale epileptic networks and propagate to regions that are not functionally altered but are recruited by epileptiform discharges. In preclinical models of focal epilepsy, the thalamus is recruited by cortical onset seizures, but it remains to be demonstrated in clinical studies. In this pilot study, the authors investigate whether seizures with onset within and outside the mesial temporal structures are detected in the anterior thalamus (ATN). METHODS: After written consent, three subjects with suspected temporal lobe epilepsy undergoing stereotactic electrode implantation were recruited prospectively for thalamocortical depth EEG recordings. Three seizure detection metrics (line length-LL, Laplace operator-Lap; Teager energy-TE) were studied within the seizure onset zone and ATN. RESULTS: The LL, Lap, and TE metrics detected 40 (95%) seizures each in the ATN before the behavioral manifestation. Rates of detection in the seizure onset zone were 40 (95%), 42 (100%), and 41 (98%), respectively. The mean detection latency in ATN from SOZ ranged from 0.25 to 5.17 s. Seizures were localized to amygdala-hippocampus, temporal pole, anterior insula and superior temporal gyrus. CONCLUSIONS: The pilot study demonstrates that seizures in mesial temporal and temporal-plus epilepsies (i.e., temporoperisylvian) can be detected reliably in the ATN. Further studies are needed to validate these findings.

High-frequency stimulation of anterior nucleus of thalamus desynchronizes epileptic network in humans.

Epilepsy has been classically seen as a brain disorder resulting from abnormally enhanced neuronal excitability and synchronization. Although it has been described since antiquity, there are still significant challenges achieving the therapeutic goal of seizure freedom. Deep brain stimulation of the anterior nucleus of the thalamus has emerged as a promising therapy for focal drug-resistant epilepsy; the basic mechanism of action, however, remains unclear. Here, we show that desynchronization is a potential mechanism of deep brain stimulation of the anterior nucleus of the thalamus by studying local field potentials recordings from the cortex during high-frequency stimulation (130 Hz) of the anterior nucleus of the thalamus in nine patients with drug-resistant focal epilepsy. We demonstrate that high-frequency stimulation applied to the anterior nucleus of the thalamus desynchronizes ipsilateral hippocampal background electrical activity over a broad frequency range, and reduces pathological epileptic discharges including interictal spikes and high-frequency oscillations. Furthermore, high-frequency stimulation of the anterior nucleus of the thalamus is capable of decoupling large-scale neural activity involving the hippocampus and distributed cortical areas. We found that stimulation frequencies ranging from 15 to 45 Hz were associated with synchronization of hippocampal local field potentials, whereas higher frequencies (>45 Hz) promoted desynchronization of ipsilateral hippocampal activity. Moreover, reciprocal effective connectivity between the anterior nucleus of the thalamus and the hippocampus was demonstrated by hippocampal-thalamic evoked potentials and thalamic-hippocampal evoked potentials. In summary, high-frequency stimulation of the anterior nucleus of the thalamus is shown to desynchronize focal and large-scale epileptic networks, and here is proposed as the mechanism for reducing seizure generation and propagation. Our data also demonstrate position-specific correlation between deep brain stimulation applied to the anterior nucleus of the thalamus and patients with temporal lobe epilepsy and seizure onset zone within the Papaz circuit or limbic system. Our observation may prove useful for guiding electrode implantation to increase clinical efficacy.

Phase-amplitude coupling within the anterior thalamic nuclei during seizures.

Cross-frequency phase-amplitude coupling (cfPAC) subserves an integral role in the hierarchical organization of interregional neuronal communication and is also expressed by epileptogenic cortex during seizures. Here, we sought to characterize patterns of cfPAC expression in the anterior thalamic nuclei during seizures by studying extra-operative recordings in patients implanted with deep brain stimulation electrodes for intractable epilepsy. Nine seizures from two patients were analyzed in the peri-ictal period. CfPAC was calculated using the modulation index and interregional functional connectivity was indexed using the phase-locking value. Statistical analysis was performed within subjects on the basis of nonparametric permutation and corrected with Gaussian field theory. Five of the nine analyzed seizures demonstrated significant cfPAC. Significant cfPAC occurred during the pre-ictal and ictal periods in three seizures, as well as the postictal windows in four seizures. The preferred phase at which cfPAC occurred differed 1) in space, between the thalami of the epileptogenic and nonepileptogenic hemispheres; and 2) in time, at seizure termination. The anterior thalamic nucleus of the epileptogenic hemisphere also exhibited altered interregional phase-locking synchrony concurrent with the expression of cfPAC. By analyzing extraoperative recordings from the anterior thalamic nuclei, we show that cfPAC associated with altered interregional phase synchrony is lateralized to the thalamus of the epileptogenic hemisphere during seizures. Electrophysiological differences in cfPAC, including preferred phase of oscillatory interactions may be further investigated as putative targets for individualized neuromodulation paradigms in patients with drug-resistant epilepsy. NEW & NOTEWORTHY The association between fast brain activity and slower oscillations is an integral mechanism for hierarchical neuronal communication, which is also manifested in epileptogenic cortex. Our data suggest that the same phenomenon occurs in the anterior thalamic nuclei during seizures. Further, the preferred phase of modulation shows differences in space, between the epileptogenic and nonepileptogenic hemispheres and time, as seizures terminate. Our data encourage the study of cross-frequency coupling for targeted, individualized closed-loop stimulation paradigms.

Neurodegeneration and NLRP3 inflammasome expression in the anterior thalamus of SOD1(G93A) ALS mice.

Nowadays, amyotrophic lateral sclerosis (ALS) is considered as a multisystem disorder, characterized by a primary degeneration of motor neurons as well as neuropathological changes in non-motor regions. Neurodegeneration in subcortical areas, such as the thalamus, are believed to contribute to cognitive and behavioral abnormalities in ALS patients. In the present study, we investigated neurodegenerative changes including neuronal loss and glia pathology in the anterodorsal thalamic nucleus (AD) of SOD1(G93A) mice, a widely used animal model for ALS. We detected massive dendrite swelling and neuronal loss in SOD1(G93A) animals, which was accompanied by a mild gliosis. Furthermore, misfolded SOD1 protein and autophagy markers were accumulating in the AD. Since innate immunity and activation inflammasomes seem to play a crucial role in ALS, we examined protein expression of Nod-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a caspase-1 recruitment domain (ASC) and the cytokine interleukin 1 beta (IL1ß) in AD glial cells and neurons. NLRP3 and ASC were significantly up-regulated in the AD of SOD1(G93A) mice. Finally, co-localization studies revealed expression of NLRP3, ASC and IL1ß in neurons. Our study yielded two main findings: (i) neurodegenerative changes already occur at an early symptomatic stage in the AD and (ii) increased inflammasome expression may contribute to neuronal cell death. In conclusion, neurodegeneration in the anterior thalamus may critically account for cognitive changes in ALS pathology.

Chemically activated luminopsins allow optogenetic inhibition of distributed nodes in an epileptic network for non-invasive and multi-site suppression of seizure activity.

Although optogenetic techniques have proven to be invaluable for manipulating and understanding complex neural dynamics over the past decade, they still face practical and translational challenges in targeting networks involving multiple, large, or difficult-to-illuminate areas of the brain. We utilized inhibitory luminopsins to simultaneously inhibit the dentate gyrus and anterior nucleus of the thalamus of the rat brain in a hardware-independent and cell-type specific manner. This approach was more effective at suppressing behavioral seizures than inhibition of the individual structures in a rat model of epilepsy. In addition to elucidating mechanisms of seizure suppression never directly demonstrated before, this work also illustrates how precise multi-focal control of pathological circuits can be advantageous for the treatment and understanding of disorders involving broad neural circuits such as epilepsy.

Anterior thalamic nuclei deep brain stimulation reduces disruption of the blood-brain barrier, albumin extravasation, inflammation and apoptosis in kainic acid-induced epileptic rats.

Objective The therapeutic efficacy of anterior thalamic nuclei deep brain stimulation (ATN-DBS) against seizures has been largely accepted; however, the effects of ATN-DBS on disruption of the blood-brain barrier (BBB), albumin extravasation, inflammation and apoptosis still remain unclear. Methods Rats were distributed into four treatment groups: physiological saline (PS, N = 12), kainic acid (KA, N = 12), KA-sham-DBS (N = 12) and KA-DBS (N = 12). Seizures were monitored using video-electroencephalogram (EEG). One day after surgery, all rats were sacrificed. Then, samples were prepared for quantitative real-time PCR (qPCR), western blot, immunofluorescence (IF) staining, and transmission electron microscopy to evaluate the disruption of the BBB, albumin extravasation, inflammation, and apoptosis. Result Because of the KA injection, the disruption of the BBB, albumin extravasation, inflammation and apoptosis were more severe in the KA and the KA-sham-DBS groups compared to the PS group (all Ps < 0.05 or < 0.01). The ideal outcomes were observed in the KA-DBS group. ATN-DBS produced a 46.3% reduction in seizure frequency and alleviated the disruption of the BBB, albumin extravasation, inflammatory reaction and apoptosis in comparison to the KA-sham-DBS group (all Ps < 0.05 or < 0.01). Conclusion (1) Seizures can be reduced using ATN-DBS in the epileptogenic stage. (2) ATN-DBS can reduce the disruption of the BBB and albumin extravasation. (3) ATN-DBS has an anti-inflammatory effect in epileptic models.

Deep brain stimulation of the anterior nucleus of the thalamus reverses the gene expression of cytokines and their receptors as well as neuronal degeneration in epileptic rats.

BACKGROUND: Deep brain stimulation of the anterior nucleus of the thalamus (ANT-DBS) is effective in seizure control. However, the mechanisms remain unclear. METHODS: Sixty-four rats were randomly assigned to the control group, the kainic acid (KA) group, the sham-DBS group and the DBS group. Video-electroencephalogram (EEG) was used to monitor seizures. Quantitative real time PCR (qPCR) was applied for detecting interleukin-1 beta (IL-1ß), IL-1 receptor (IL-1R), IL-6, IL-6 receptor (IL-6R), gp130, tumor necrosis factor-alpha (TNF-α), TNF-receptor 1 (TNF-R1) and TNF-receptor 2 (TNF-R2) expression 12h after the establishment of an epileptic model. The neuronal structural degeneration in the hippocampus was evaluated with transmission electron microscopy (TEM) at this same time point. RESULTS: The seizure frequency was 48.6% lower in the DBS group compared with the sham-DBS group (P<0.01). The expression of IL-1ß, IL-1R, IL-6, IL-6R, gp130, TNF-α and TNF-R1 was elevated in both the KA and the sham group compared with the control group (all Ps<0.01). Additionally, ANT-DBS was able to reverse this gene expression pattern in the DBS group compared with the sham-DBS group (all Ps<0.01). There was no significant difference in TNF-R2 expression among the four groups. The neuronal structural degeneration in the KA group and the sham-DBS group was more severe than that in the control group (injury scores, all Ps<0.01). ANT-DBS was also capable of relieving the degeneration compared with the sham-DBS group (injury score, P<0.01). CONCLUSIONS: This study demonstrated that ANT-DBS can reduce seizure frequency in the early stage in epileptic rats as well as relieve the pro-inflammatory state and neuronal injury, which may be one of the most effective mechanisms of ANT-DBS against epileptogenesis.