Evidence for the role of magnetic source imaging in the presurgical evaluation of refractory epilepsy patients

Magnetoencephalography (MEG) in the field of epilepsy has multiple advantages; just like electroencephalography (EEG), MEG is able to measure the epilepsy specific information (i.e., the brain activity reflecting seizures and/or interictal epileptiform discharges) directly, non-invasively and with a very high temporal resolution (millisecond-range). In addition MEG has a unique sensitivity for tangential sources, resulting in a full picture of the brain activity when combined with EEG. It accurately allows to perform source imaging of focal epileptic activity and functional cortex and shows a specific high sensitivity for a source in the neocortex. In this paper the current evidence and practice for using magnetic source imaging of focal interictal and ictal epileptic activity during the presurgical evaluation of drug resistant patients is being reviewed

Event-related potentials reveal preserved attention allocation but impaired emotion regulation in patients with epilepsy and comorbid negative affect

Patients with epilepsy have a high prevalence of comorbid mood disorders. This study aims to evaluate whether negative affect in epilepsy is associated with dysfunction of emotion regulation. Event-related potentials (ERPs) are used in order to unravel the exact electrophysiological time course and investigate whether a possible dysfunction arises during early (attention) and/or late (regulation) stages of emotion control. Fifty epileptic patients with (n = 25) versus without (n = 25) comorbid negative affect plus twenty-five matched controls were recruited. ERPs were recorded while subjects performed a face- or house-matching task in which fearful, sad or neutral faces were presented either at attended or unattended spatial locations. Two ERP components were analyzed: the early vertex positive potential (VPP) which is normally enhanced for faces, and the late positive potential (LPP) that is typically larger for emotional stimuli. All participants had larger amplitude of the early face-sensitive VPP for attended faces compared to houses, regardless of their emotional content. By contrast, in patients with negative affect only, the amplitude of the LPP was significantly increased for unattended negative emotional expressions. These VPP results indicate that epilepsy with or without negative affect does not interfere with the early structural encoding and attention selection of faces. However, the LPP results suggest abnormal regulation processes during the processing of unattended emotional faces in patients with epilepsy and comorbid negative affect. In conclusion, this ERP study reveals that early object-based attention processes are not compromised by epilepsy, but instead, when combined with negative affect, this neurological disease is associated with dysfunction during the later stages of emotion regulation. As such, these new neurophysiological findings shed light on the complex interplay of epilepsy with negative affect during the processing of emotional visual stimuli and in turn might help to better understand the etiology and maintenance of mood disorders in epilepsy

Neurophysiological investigations of drug resistant epilepsy patients treated with vagus nerve stimulation to differentiate responders from non-responders

Background and purpose In patients treated with vagus nerve stimulation (VNS) for drug resistant epilepsy (DRE), up to a third of patients will eventually not respond to the therapy. As VNS therapy requires surgery for device implantation, prediction of response prior to surgery is desirable. It is hypothesized that neurophysiological investigations related to the mechanisms of action of VNS may help to differentiate VNS responders from non-responders prior to the initiation of therapy. Methods In a prospective series of DRE patients, polysomnography, heart rate variability (HRV) and cognitive event related potentials were recorded. Polysomnography and HRV were repeated after 1 year of treatment with VNS. Polysomnography, HRV and cognitive event related potentials were compared between VNS responders (>= 50% reduction in seizure frequency) and non-responders. Results Fifteen out of 30 patients became VNS responders after 1 year of VNS treatment. Prior to treatment with VNS, the amount of deep sleep (NREM 3), the HRV high frequency (HF) power and the P3b amplitude were significantly different in responders compared to non-responders (P = 0.007; P = 0.001; P = 0.03). Conclusion Three neurophysiological parameters, NREM 3, HRV HF and P3b amplitude, were found to be significantly different in DRE patients who became responders to VNS treatment prior to initiation of their treatment with VNS. These non-invasive recordings may be used as characteristics for response in future studies and help avoid unsuccessful implantations. Mechanistically these findings may be related to changes in brain regions involved in the so-called vagal afferent network

Transcutaneous vagus nerve stimulation does not affect verbal memory performance in healthy volunteers

Introduction: Invasive vagus nerve stimulation (VNS) improves word recognition memory in patients with epilepsy. Recent studies with transcutaneous VNS (tVNS) have also shown positive effects on various subdomains of cognitive functioning in healthy volunteers. In this randomized, controlled, crossover study, we investigated the effect of tVNS on a word recognition memory paradigm in healthy volunteers to further investigate the potential of tVNS in the treatment of cognitive disorders. Methods: We included 41 healthy participants aged between 18 and 30 years (young age group) and 24 healthy participants aged between 45 and 80 years (older age group). Each participant completed a word recognition memory paradigm during three different conditions: true tVNS, sham, and control. During true tVNS, stimulation was delivered at the cymba conchae. Sham stimulation was delivered by stimulating the earlobe. In the control condition, no stimulation was given. In each condition, participants were asked to remember highlighted words from three test paragraphs. Accuracy scores were calculated for immediate recall after each test paragraph and for delayed recognition at the end of the paradigm. We hypothesized that highlighted words from paragraphs in the true tVNS condition would be more accurately recalled and/or recognized compared to highlighted words from paragraphs in the sham or control condition. Results: In this randomized study, tVNS did not affect the accuracy scores for immediate recall or delayed recognition in both age groups. The younger group showed significantly higher accuracy scores than the older group. The accuracy scores improved over time, and the most recently learned words were better recognized. Participants rated true tVNS as significantly more painful; however, pain was not found to affect accuracy scores. Conclusion: In this study, tVNS did not affect verbal memory performance in healthy volunteers. Our results could not replicate the positive effects of invasive VNS on word recognition memory in epilepsy patients. Future research with the aim of improving cognitive function should focus on the rational identification of optimized and individualized stimulation settings primarily in patients with cognitive deficits

Soft, comfortable polymer dry electrodes for high quality ECG and EEG recording

Conventional gel electrodes are widely used for biopotential measurements, despite important drawbacks such as skin irritation, long set-up time and uncomfortable removal. Recently introduced dry electrodes with rigid metal pins overcome most of these problems; however, their rigidity causes discomfort and pain. This paper presents dry electrodes offering high user comfort, since they are fabricated from EPDM rubber containing various additives for optimum conductivity, flexibility and ease of fabrication. The electrode impedance is measured on phantoms and human skin. After optimization of the polymer composition, the skin-electrode impedance is only similar to 10 times larger than that of gel electrodes. Therefore, these electrodes are directly capable of recording strong biopotential signals such as ECG while for low-amplitude signals such as EEG, the electrodes need to be coupled with an active circuit. EEG recordings using active polymer electrodes connected to a clinical EEG system show very promising results: alpha waves can be clearly observed when subjects close their eyes, and correlation and coherence analyses reveal high similarity between dry and gel electrode signals. Moreover, all subjects reported that our polymer electrodes did not cause discomfort. Hence, the polymer-based dry electrodes are promising alternatives to either rigid dry electrodes or conventional gel electrodes

Optimized parameters for transducing the locus coeruleus using canine adenovirus type 2 (CAV2) vector in rats for chemogenetic modulation research

Introduction The locus coeruleus noradrenergic (LC-NA) system is studied for its role in various neurological and psychiatric disorders such as epilepsy and Major Depression Dissorder. Chemogenetics is a powerful technique for specific manipulation of the LC to investigate its functioning. Local injection of AAV2/7 viral vectors has limitations with regards to efficiency and specificity of the transduction, potentially due to low tropism of AAV2/7 for LC neurons. In this study we used a canine adenovirus type 2 (CAV2) vector with different volumes and viral particle numbers to achieve high and selective expression of hM3Dq, an excitatory Designer Receptor Exclusively Activated by Designer Drugs (DREADD), for chemogenetic modulation of LC neurons. Methods Adult male Sprague-Dawley rats were injected in the LC with different absolute numbers of CAV2-PRSx8-hM3Dq-mCherry physical particles (0.1E9, 1E9, 5E9,10E9, or 20E9 pp) using different volumes (LowV = 3 nl x 300 nl, MediumV = 3 x 600 nl, HighV = 3 x 1200 nl). Two weeks post-injection, double-labeling immunohistochemistry for dopamine beta hydroxylase (DBH) and mCherry was performed to determine hM3Dq expression and its specificity for LC neurons. The size of the transduced LC was compared to the contralateral LC to identify signs of toxicity. Results Administration of Medium volume (3 x 600 nl) and 1E9 particles resulted in high expression levels with 87.3 +/- 9.8% of LC neurons expressing hM3Dq, but low specificity with 36.2 +/- 17.3% of hM3Dq expression in non-LC neurons. The most diluted conditions (Low volume_0.1E pp and Medium Volume_0.1E pp) presented similar high transduction of LC neurons (70.9 +/- 12.7 and 77.2 +/- 9.8%) with lower aspecificity (5.5 +/- 3.5 and 4.0 +/- 1.9%, respectively). Signs of toxicity were observed in all undiluted conditions as evidenced by a decreased size of the transduced LC. Conclusion This study identified optimal conditions (Low and Medium Volume with 0.1E9 particles of CAV2-PRSx8-hM3Dq-mCherry) for safe and specific transduction of LC neurons with excitatory DREADDs to study the role of the LC-NA system in health and disease