Evaluation of Paroxysmal Events in Critically Ill Patients: Relationship of Primary Diagnosis to Long-Term Electroencephalogram Yield.

Continuous EEG (cEEG) is indicated for the workup of paroxysmal events. We aimed to assess whether primary admission diagnoses predict the yield of cEEG when ordered for evaluating paroxysmal events. We identified patients in the ICU who underwent at least 6 hours of cEEG monitoring to evaluate paroxysmal events. Primary admission diagnoses were categorized into neurological or non-neurological conditions. cEEG results were dichotomized into presence or absence of epileptiform discharges. We identified 159 recordings that were obtained for the evaluation of paroxysmal events. Most patients (n = 100, 63%) were admitted with primary admission diagnoses of neurological disorders, such as ischemic stroke, or intracranial hemorrhage. We found that patients with primary neurological conditions were more likely to have brain surgeries, abnormal brain imaging, and focal neurological deficits on examination compared to those with primary non-neurological conditions. However, there was no significant difference in the prevalence of epileptiform discharges in cEEG among patients with primary diagnoses of neurological or non-neurological disorders. These results suggest that cEEG is often necessary to evaluate paroxysmal events, even among patients without primary neurological disorders.

Towards optimizing single pulse electrical stimulation: High current intensity, short pulse width stimulation most effectively elicits evoked potentials.

BACKGROUND: While single pulse electrical stimulation (SPES) is increasingly used to study effective connectivity, the effects of varying stimulation parameters on the resulting cortico-cortical evoked potentials (CCEPs) have not been systematically explored. OBJECTIVE: We sought to understand the interacting effects of stimulation pulse width, current intensity, and charge on CCEPs through an extensive testing of this parameter space and analysis of several response metrics. METHODS: We conducted SPES in 11 patients undergoing intracranial EEG monitoring using five combinations of current intensity (1.5, 2.0, 3.0, 5.0, and 7.5 mA) and pulse width at each of three charges (0.750, 1.125, and 1.500 µC/phase) to study how CCEP amplitude, distribution, latency, morphology, and stimulus artifact amplitude vary with each parameter. RESULTS: Stimulations with a greater charge or a greater current intensity and shorter pulse width at a given charge generally resulted in greater CCEP amplitudes and spatial distributions, shorter latencies, and increased waveform correlation. These effects interacted such that stimulations with the lowest charge and highest current intensities resulted in greater response amplitudes and spatial distributions than stimulations with the highest charge and lowest current intensities. Stimulus artifact amplitude increased with charge, but this could be mitigated by using shorter pulse widths. CONCLUSIONS: Our results indicate that individual combinations of current intensity and pulse width, in addition to charge, are important determinants of CCEP magnitude, morphology, and spatial extent. Together, these findings suggest that high current intensity, short pulse width stimulations are optimal SPES settings for eliciting strong and consistent responses while minimizing charge.

Functional anomaly mapping lateralizes temporal lobe epilepsy with high accuracy in individual patients.

Mesial temporal lobe epilepsy (mTLE) is associated with variable dysfunction beyond the temporal lobe. We used functional anomaly mapping (FAM), a multivariate machine learning approach to resting state fMRI analysis to measure subcortical and cortical functional aberrations in patients with mTLE. We also examined the value of individual FAM in lateralizing the hemisphere of seizure onset in mTLE patients. Methods: Patients and controls were selected from an existing imaging and clinical database. After standard preprocessing of resting state fMRI, time-series were extracted from 400 cortical and 32 subcortical regions of interest (ROIs) defined by atlases derived from functional brain organization. Group-level aberrations were measured by contrasting right (RTLE) and left (LTLE) patient groups to controls in a support vector regression models, and tested for statistical reliability using permutation analysis. Individualized functional anomaly maps (FAMs) were generated by contrasting individual patients to the control group. Half of patients were used for training a classification model, and the other half for estimating the accuracy to lateralize mTLE based on individual FAMs. Results: Thirty-two right and 14 left mTLE patients (33 with evidence of hippocampal sclerosis on MRI) and 94 controls were included. At group levels, cortical regions affiliated with limbic and somatomotor networks were prominent in distinguishing RTLE and LTLE from controls. At individual levels, most TLE patients had high anomaly in bilateral mesial temporal and medial parietooccipital default mode regions. A linear support vector machine trained on 50% of patients could accurately lateralize mTLE in remaining patients (median AUC =1.0 [range 0.97-1.0], median accuracy = 96.87% [85.71-100Significance: Functional anomaly mapping confirms widespread aberrations in function, and accurately lateralizes mTLE from resting state fMRI. Future studies will evaluate FAM as a non-invasive localization method in larger datasets, and explore possible correlations with clinical characteristics and disease course.

Association between postictal EEG suppression, postictal autonomic dysfunction, and sudden unexpected death in epilepsy: Evidence from intracranial EEG.

OBJECTIVE: The association between postictal electroencephalogram (EEG) suppression (PES), autonomic dysfunction, and Sudden Unexpected Death in Epilepsy (SUDEP) remains poorly understood. We compared PES on simultaneous intracranial and scalp-EEG and evaluated the association of PES with postictal heart rate variability (HRV) and SUDEP outcome. METHODS: Convulsive seizures were analyzed in patients with drug-resistant epilepsy at 5 centers. Intracranial PES was quantified using the Hilbert transform. HRV was quantified using root mean square of successive differences of interbeat intervals, low-frequency to high-frequency power ratio, and RR-intervals. RESULTS: There were 64 seizures from 63 patients without SUDEP and 11 seizures from 6 SUDEP patients. PES occurred in 99% and 87% of seizures on intracranial-EEG and scalp-EEG, respectively. Mean PES duration in intracranial and scalp-EEG was similar. Intracranial PES was regional (<90% of channels) in 46% of seizures; scalp PES was generalized in all seizures. Generalized PES showed greater decrease in postictal parasympathetic activity than regional PES. PES duration and extent were similar between patients with and without SUDEP. CONCLUSIONS: Regional intracranial PES can be present despite scalp-EEG demonstrating generalized or no PES. Postictal autonomic dysfunction correlates with the extent of PES. SIGNIFICANCE: Intracranial-EEG demonstrates changes in autonomic regulatory networks not seen on scalp-EEG.

Deep Brain Stimulation of the Centromedian Nucleus of the Thalamus for Lennox-Gastaut Syndrome: A Systematic Review and Individual Patient Data Analysis.

BACKGROUND: Lennox-Gastaut syndrome (LGS) is a severe childhood-onset pharmacoresistant epilepsy. Deep brain stimulation (DBS) of the centromedian nucleus of the thalamus (CMN) has been utilized. OBJECTIVE: To conduct a systematic review and individual patient data (IPD) analysis to characterize outcomes of DBS of CMN in LGS. METHODS: PubMed, Embase, and Scopus were searched per Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Articles were screened by title/abstract then full text. Included articles were reviewed for bibliographic, demographic, and outcome data. IPD were extracted from studies providing IPD for all patients. RESULTS: Of 72 resultant articles, 10 studies (114 patients) were included. Six of 7 studies reporting the outcome of ≥50% seizure reduction indicated that ≥50% of patients achieved this, with improved functional ability. Seizure freedom rate was generally <10%. Six studies with 47 patients provided IPD. The mean ages at epilepsy onset and CMN DBS were 3.9 ± 4.5 years and 17.4 ± 8.8 years, respectively. Nineteen of 41 (46.3%) patients had positive MRI findings. Seizure types included atypical absence in 39 (83.0%) patients, generalized tonic-clonic in 32 (68.1%), tonic in 22 (46.8%), and atonic in 20 (42.6%). Thirty-eight (80.9%) patients experienced ≥50% reduction in seizure frequency, and only 3 (6.4%) experienced seizure freedom. The mean seizure reduction was 62.9% ± 31.2% overall. Quality of life improved in 30/34 (88.2%) and was unchanged in the remainder (11.8%). The complication rate was 2/41 (4.9%). The mean length of follow-up was 19.8 ± 26.1 months (IQR: 4-18 months). CONCLUSION: Limited data indicate that DBS of the CMN may be effective and safe for people with LGS.

The neural networks underlying the illusion of time dilation: case study and literature survey.

This is the first known case report of a profound illusionary time dilation produced by direct electrical cortical stimulation. The patient with drug-resistant epilepsy was undergoing invasive EEG evaluation for the localization of the focus prior to resection. Stimulation of the non-dominant claustrum/insula and inferior right frontal gyrus correlated with the equivalent of a pacemaker of an internal clock in the brain. The site exhibited strong outflow connectivity with a wide region of the right fronto-parietal executive network and pre-motor system. The patient described the experience as unique and fascinating, and underwent resection involving the face motor area where seizures arose from, with a substantial decrease in seizure burden >90%. Extensive brain networks are employed in evaluation/assessment of time, which may be modulated via electrical stimulation. This is the first of such an incident. Further studies may investigate the potential benefit of neuromodulation of these brain regions in the management of conditions in which time-perception may be impaired.

Continuous Electroencephalogram Evaluation of Paroxysmal Events in Critically Ill Patients: Diagnostic Yield and Impact on Clinical Decision Making.

BACKGROUND: Continuous electroencephalogram (cEEG) monitoring has been widely used in the intensive care unit (ICU) for the evaluation of patients in the ICU with altered consciousness to detect nonconvulsive seizures. We investigated the yield of cEEG when used to evaluate paroxysmal events in patients in the ICU and assessed the predictors of a diagnostic findings. The clinical impact of cEEG was also evaluated in this study. METHODS: We identified patients in the ICU who underwent cEEG monitoring (> 6 h) to evaluate paroxysmal events between January 1, 2018, and December 31, 2019. We extracted patient demographics, medical history, neurological examination, brain imaging results, and the description of the paroxysmal events that necessitated the monitoring. We dichotomized the cEEG studies into those that captured habitual nonepileptic events or revealed epileptiform discharges (ictal or interictal), i.e., those considered to be of positive diagnostic yield (Y +), and those studies that did not show those findings (negative diagnostic yield, Y -). We also assessed the clinical impact of cEEG by documenting changes in administered antiseizure medication (ASM) before and after the cEEG. RESULTS: We identified 159 recordings that were obtained for the indication of paroxysmal events, of which abnormal movements constituted the majority (n = 123). For the remaining events (n = 36), descriptions included gaze deviations, speech changes, and sensory changes. Twenty-nine percent (46 of 159) of the recordings were Y + , including the presence of ictal or interictal epileptiform discharges (n = 33), and captured habitual nonepileptic events (n = 13). A history of epilepsy was the only predictor of the study outcome. Detection of abnormal findings occurred within 6 h of the recording in most patients (30 of 46, 65%). Overall, cEEG studies led to 49 (31%) changes in ASM administration. The changes included dosage increases or initiation of ASM in patients with epileptiform discharges (n = 28) and reduction or elimination of ASM in patients with either habitual nonepileptic events (n = 5) or Y - cEEG studies (n = 16). CONCLUSIONS: Continuous electroencephalogram monitoring is valuable in evaluating paroxysmal events, with a diagnostic yield of 29% in critically ill patients. A history of epilepsy predicts diagnostic studies. Both Y + and Y - cEEG studies may directly impact clinical decisions by leading to ASMs changes.

The Temporal Lobe as a Symptomatogenic Zone in Medial Parietal Lobe Epilepsy.

Some surgical failures after temporal lobe epilepsy surgery may be due to the presence of an extratemporal epileptogenic zone. Of particular interest is the medial parietal lobe due to its robust connectivity with mesial temporal structures. Seizures in that area may be clinically silent before propagating to the symptomatogenic temporal lobe. In this paper, we present an overview of the anatomical connectivity, semiology, radiology, electroencephalography, neuropsychology, and outcomes in medial parietal lobe epilepsy. We also present two illustrative cases of seizures originating from the precuneus and the posterior cingulate cortex. We conclude that the medial parietal lobe should be strongly considered for sampling by intracranial electrodes in individuals with nonlesional temporal lobe epilepsy, especially if scrutinizing the presurgical data produces discordant findings.

Low-frequency stimulation of a fiber tract in bilateral temporal lobe epilepsy.

OBJECTIVE: Pharmacoresistant bilateral mesial temporal lobe epilepsy often implies poor resective surgical candidacy. Low-frequency stimulation of a fiber tract connected to bilateral hippocampi, the fornicodorsocommissural tract, has been shown to be safe and efficacious in reducing seizures in a previous short-term study. Here, we report a single-blinded, within-subject control, long-term deep-brain stimulation trial of low-frequency stimulation of the fornicodorsocommissural tract in bilateral mesial temporal lobe epilepsy. Outcomes of interest included safety with respect to verbal memory scores and reduction of seizure frequency. METHODS: Our enrollment goal was 16 adult subjects to be randomized to 2-Hz or 5-Hz low-frequency stimulation of the fornicodorsocommissural tract starting at 2 mA. The study design consisted of four two-month blocks of stimulation with a 50%-duty cycle, alternating with two-month blocks of no stimulation. RESULTS: We terminated the study after enrollment of five subjects due to slow accrual. Fornicodorsocommissural tract stimulation elicited bilateral hippocampal evoked responses in all subjects. Three subjects underwent implantation of pulse generators and long-term low-frequency stimulation with mean monthly seizures of 3.14 ±â€¯2.67 (median 3.0 [IQR 1-4.0]) during stimulation-off blocks, compared with 0.96 ±â€¯1.23 (median 1.0 [IQR 0-1.0]) during stimulation-on blocks (p = 0.0005) during the blinded phase. Generalized Estimating Equations showed that low-frequency stimulation reduced monthly seizure-frequency by 0.71 per mA (p < 0.001). Verbal memory scores were stable with no psychiatric complications or other adverse events. SIGNIFICANCE: The results demonstrate feasibility of stimulating both hippocampi using a single deep-brain stimulation electrode in the fornicodorsocommissural tract, efficacy of low-frequency stimulation in reducing seizures, and safety as regards verbal memory.

Common functional connectivity alterations in focal epilepsies identified by machine learning.

OBJECTIVE: This study was undertaken to identify shared functional network characteristics among focal epilepsies of different etiologies, to distinguish epilepsy patients from controls, and to lateralize seizure focus using functional connectivity (FC) measures derived from resting state functional magnetic resonance imaging (MRI). METHODS: Data were taken from 103 adult and 65 pediatric focal epilepsy patients (with or without lesion on MRI) and 109 controls across four epilepsy centers. We used three whole-brain FC measures: parcelwise connectivity matrix, mean FC, and degree of FC. We trained support vector machine models with fivefold cross-validation (1) to distinguish patients from controls and (2) to lateralize the hemisphere of seizure onset in patients. We reported the regions and connections with the highest importance from each model as the common FC differences between the compared groups. RESULTS: FC measures related to the default mode and limbic networks had higher importance relative to other networks for distinguishing epilepsy patients from controls. In lateralization models, regions related to somatosensory, visual, default mode, and basal ganglia showed higher importance. The epilepsy versus control classification model trained using a 400-parcel connectivity matrix achieved a median testing accuracy of 75.6% (median area under the curve [AUC] = .83) in repeated independent testing. Lateralization accuracy using the 400-parcel connectivity matrix reached a median accuracy of 64.0% (median AUC = .69). SIGNIFICANCE: Machine learning models revealed common FC alterations in a heterogeneous group of patients with focal epilepsies. The distribution of the most altered regions supports the hypothesis that shared functional alteration exists beyond the seizure onset zone and its epileptic network. We showed that FC measures can distinguish patients from controls, and further lateralize focal epilepsies. Future studies are needed to confirm these findings by using larger numbers of epilepsy patients.

Multifocal myoclonus as a presentation of levetiracetam toxicity.

BACKGROUND: Levetiracetam (LEV) is widely used for treatment of focal and myoclonic seizures, but reports of LEV toxicity are scarce. Here, we report a rare case of multifocal myoclonus due to LEV toxicity in a patient with chronic renal insufficiency. CASE PRESENTATION: A 52-year-old woman with history of chronic kidney disease was admitted to the ICU for sedation and intubation after a cardiac arrest. She developed nonconvulsive status epilepticus that resolved after administration of propofol while receiving LEV 1500 mg twice a day. After holding the propofol infusion, the patient started having multifocal myoclonic jerks, documented on video-EEG recordings with a supratherapeutic level of LEV. After discontinuation of LEV, the myoclonus resolved. CONCLUSION: This is a unique manifestation of LEV toxicity, which has been scarce in the literature. It suggests an inverted U-shaped dose-response of the antimyoclonic effect of LEV.

Seizure recurrence after prolonged seizure control: Patterns and risk factors.

OBJECTIVE: To identify the patterns and possible predictors of seizure recurrence after durable seizure freedom during maintenance of anti-seizure medication (ASM) treatment. METHODS: We conducted a retrospective longitudinal study that identified all adult individuals with epilepsy (IWE) at the George Washington University outpatient epilepsy clinic between 1/1/2014 and 12/31/2016 who had been seizure free for at least 2 years. We followed up the patients until 5/30/2020 for seizure recurrence. The data were analyzed using survival analysis, univariate analysis, and multivariate regression with Cox proportional hazard model. Outcomes were dichotomized into seizure relapse and seizure freedom. The total number of relapses and triggers of the initial relapse for individual patient were also analyzed. RESULTS: This single-center cohort consisted of 220 IWE (age 21-80) of whom 99 patients had been seizure free for 2-3 years and 121 patients had been seizure free for more than 3 years. In this cohort, 48 patients (22%) experienced at least one seizure relapse during the span of the study. Of the relapsing patients, 25 (52%) had a single seizure relapse, and 8 (15%) had frequent seizure relapses (n ≥ 5) and developed pharmacoresistance. Half of the initial seizure relapses occurred without a trigger. Among those with at least one year of follow-up after relapsing (n = 33), 29 (86%) regained seizure freedom for at least 1 year. Among 26 patients with at least 2 years of follow-up, only 14 (55%) regained at least 2 years of seizure freedom. Previous longer duration of seizure freedom and ASM monotherapy predicted less chances of seizure relapse and fewer seizure numbers after relapse. No difference in prognosis was noted among relapsing patients between those with or without triggers. SIGNIFICANCE: Patients with well-controlled epilepsy may have seizure relapses with or without identifiable triggers. Most patients regained at least 1-year seizure freedom after the initial relapse, whereas about half patients reachieved 2-year seizure remission. About 15% of the relapsing patients may subsequently develop pharmacoresistance. Prognostic factors of seizure recurrences include duration of initial seizure remission and the number of ASMs used during remission. The presence of identifiable triggers for the initial seizure relapse does not predict future outcome.

Temporal lobe epilepsy with a contralateral parietal seizure-onset zone.

Achieving sustained seizure freedom following epilepsy surgery remains a challenge in some patients. Lesional temporal lobe epilepsy (TLE), for example, in patients with mesial temporal sclerosis or other MRI abnormalities, carries a good prognosis for seizure freedom compared to significantly lower chances of seizure freedom in patients with non-lesional epilepsy. However, even in some lesional TLE cases, persistent post-operative seizures suggest seizure onset from a brain region that is clinically and electrographically silent but manifests only after propagation to the temporal lobe. A notable example of such a brain region is the parietal lobe, which has extensive connectivity to various brain regions. While certain seizure semiologies, for example, sensory seizures, suggest parietal lobe onset, some medial parietal seizures may be semiologically indistinguishable from temporal lobe seizures. Here, we report a patient with focal impaired awareness seizures that manifested semiologically and electrographically as left TLE but proved to originate from the contralateral medial parietal lobe. We discuss putative seizure propagation pathways.

Stimulating Solutions for Intractable Epilepsy.

Implantable devices for controlling medically intractable seizures nondestructively are rapidly advancing. These offer reversible, potentially, restorative options beyond traditional, surgical procedures, which rely, largely on resection or ablation of selected brain sites. Several lines of, investigation aimed at improving efficacy of these devices are discussed, ranging from identifying novel subcortical, white matter, or cell-type specific targets to engineering advances for adaptive techniques based- on continuous, dynamic system analysis.

Clinical and genomic analysis of a large Chinese family with familial cortical myoclonic tremor with epilepsy and SAMD12 intronic repeat expansion.

Objective: Our goal was to perform detailed clinical and genomic analysis of a large multigenerational Chinese family with 21 individuals showing symptoms of Familial Cortical Myoclonic Tremor with Epilepsy (FCMTE) that we have followed for over 20 years. Methods: Patients were subjected to clinical evaluation, routine EEG, and structural magnetic resonance imaging. Whole exome sequencing, repeat-primed PCR, long-range PCR, and PacBio sequencing were performed to characterize the disease-causing mutation in this family. Results: All evaluated patients manifested adult-onset seizures and presented with progressive myoclonic postural tremors starting after the third or fourth decade of life. Seizures typically diminished markedly in frequency with implementation of antiseizure medications but did not completely cease. The electroencephalogram of affected individuals showed generalized or multifocal spikes and slow wave complexes. An expansion of TTTTA motifs with addition of TTTCA motifs in intron 4 of SAMD12 was identified to segregate with the disease phenotype in this family. Furthermore, we found that the mutant allele is unstable and can undergo both contraction and expansion by changes in the number of repeat motifs each time it is passed to the next generation. The size of mutant allele varied from 5 to 5.5 kb with 549-603 copies of TTTTA and 287-343 copies of TTTCA repeat motifs in this family. Significance: Our study provides a detailed description of clinical progression of FCMTE symptoms and its management with antiseizure medications. Our method of repeat analysis by PacBio sequencing of long-range PCR products does not require high-quality DNA and hence can be easily applied to other families to elucidate any correlation between the repeat size and phenotypic variables, such as, age of onset, and severity of symptoms.

Human hippocampal connectivity is stronger in olfaction than other sensory systems.

During mammalian evolution, primate neocortex expanded, shifting hippocampal functional networks away from primary sensory cortices, towards association cortices. Reflecting this rerouting, human resting hippocampal functional networks preferentially include higher association cortices, while those in rodents retained primary sensory cortices. Research on human visual, auditory and somatosensory systems shows evidence of this rerouting. Olfaction, however, is unique among sensory systems in its relative structural conservation throughout mammalian evolution, and it is unknown whether human primary olfactory cortex was subject to the same rerouting. We combined functional neuroimaging and intracranial electrophysiology to directly compare hippocampal functional networks across human sensory systems. We show that human primary olfactory cortex-including the anterior olfactory nucleus, olfactory tubercle and piriform cortex-has stronger functional connectivity with hippocampal networks at rest, compared to other sensory systems. This suggests that unlike other sensory systems, olfactory-hippocampal connectivity may have been retained in mammalian evolution. We further show that olfactory-hippocampal connectivity oscillates with nasal breathing. Our findings suggest olfaction might provide insight into how memory and cognition depend on hippocampal interactions.

Seizure symptoms and ambulatory EEG findings: incidence of epileptiform discharges.

AIMS: Ambulatory video-EEG monitoring has been utilized as a cost-effective alternative to inpatient video-EEG monitoring for non-surgical diagnostic evaluation of symptoms suggestive of epileptic seizures. We aimed to assess incidence of epileptiform discharges in ambulatory video-EEG recordings according to seizure symptom history obtained during clinical evaluation. METHODS: This was a retrospective cohort study. We queried seizure symptoms from 9,221 consecutive ambulatory video-EEG studies in 35 states over one calendar year. We assessed incidence of epileptiform discharges for each symptom, including symptoms that conformed to a category heading, even if not included in the ILAE 2017 symptom list. We report incidences, odds ratios, and corresponding p values using Fisher's exact test and univariate logistic regression. We applied multivariable logistic regression to generate odds ratios for the six symptom categories that are controlled for the presence of other symptoms. RESULTS: History that included motor symptoms (OR=1.53) or automatisms (OR=1.42) was associated with increased occurrence of epileptiform discharges, whereas history of sensory symptoms (OR=0.76) predicted lack of epileptiform discharges. Patient-reported symptoms that were associated with increased occurrence of epileptiform discharges included lip-smacking, moaning, verbal automatism, aggression, eye-blinking, déjà vu, muscle pain, urinary incontinence, choking and jerking. On the other hand, auditory hallucination memory deficits, lightheadedness, syncope, giddiness, fibromyalgia and chronic pain predicted absence of epileptiform discharges. The majority of epileptiform discharges consisted only of interictal sharp waves or spikes. CONCLUSIONS: Our study shows that the use of ILAE 2017 symptom categories may help guide ambulatory video-EEG studies.

Epileptogenesis-induced changes of hippocampal-piriform connectivity.

OBJECTIVE: Tissue remodeling has been described in brain circuits that are involved in the generation and propagation of epileptic seizures. Human and animal studies suggest that the anterior piriform cortex (aPC) is crucial for seizure expression in focal epilepsies. Here, we investigate the effect of kainic-acid (KA)-induced seizures on the effective connectivity of the aPC with bilateral hippocampal CA3 regions using cerebro-cerebral evoked potentials (CCEPs). METHODS: Adult male Sprague-Dawley rats were implanted with a tripolar electrode in the left aPC for stimulation and recording, and with unipolar recording electrodes in bilateral CA3 regions. Single pulse stimulations were given to the aPC and CCEPs were averaged before KA injections and after the emergence of spontaneous recurrent seizures (SRS). Similar recordings at equivalent time intervals were obtained from animals that received saline injections instead of KA (controls). RESULTS: In the experimental group, the percentage change of increased amplitude of the contralateral (but not ipsilateral) CA3 CCEPs between pre-KA injection and after the emergence of SRS was significantly greater than in controls. No significant single-pulse-induced spectral change responses were observed in either epileptic or control rats when comparing pre- and post-stimulus time intervals. Also, we found no correlation between seizure frequency and the extent of amplitude changes in the CCEPs. CONCLUSIONS: In the KA model, epileptogenesis results in plastic changes that manifest as an amplification of evoked potential amplitudes recorded in the contralateral hippocampus in response to single-pulse stimulation of the aPC. These results suggest epileptogenesis-induced facilitation of interhemispheric connectivity between the aPC and the hippocampus. Since the amplitude increase of the contralateral CCEP is a possible in vivo biomarker of epilepsy, any intervention (e.g. neuromodulatory) that can reverse this phenomenon may hold a potential antiepileptic efficacy.