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Purpose Vagus nerve stimulation (VNS) is an effective and well-known treatment for drug resistant epilepsy (DRE) patients since 1997, yet prediction of treatment response before implantation is subject of ongoing research. Neuroimaging and neurophysiological studies investigating the vagal afferent network in resting state documented that differences in between epilepsy patients were related to treatment response. This study investigated whether an event-related parameter, pre-ictal heart rate variability (HRV) is associated with response to VNS therapy. Methods DRE patients underwent video-electroencephalography (EEG) recording before VNS implantation. HRV parameters (time, non-linear and frequency domain) were assessed for every seizure during two 10 min timeframes: baseline (60 min before seizure onset) and pre-ictal (10 min before seizure onset). Pre-ictal HRV parameter alterations were correlated with VNS response after one year of VNS therapy and seizure characteristics (temporal/extratemporal, left/right or bilateral). Results 104 seizures from 22 patients were evaluated. Eleven patients were VNS responders with a seizure frequency reduction of ≥ 50 % after one year of VNS. In VNS responders no changes in HRV parameters were found while in VNS non-responders the time domain and non-linear HRV variables decreased significantly (p = 0.024, p = 0.005, p = 0.005) during the pre-ictal time frame. 10/11 VNS non-responders had a seizure lateralization to the left compared to 4/11 VNS responders. Conclusion VNS non-responders were characterized by a significant decrease of pre-ictal HRV (time domain/non-linear variables) suggesting a sudden autonomic imbalance probably due to an impaired central autonomic function that makes it at the same time unlikely to respond to VNS.

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.

Facilitation of object processing in the brain due to a related context (priming) can be influenced by both semantic connections and perceptual similarity. It is thus important to discern these two when evaluating the spatio-temporal dynamics of primed object processing. The repetition-priming paradigm frequently used to study perceptual priming is, however, unable to differentiate between the mentioned priming effects, possibly leading to confounded results. In the current study, we recorded brain signals from the scalp and cerebral convexity of nine patients with refractory epilepsy in response to related and unrelated image-pairs, all of which shared perceptual features while only related ones had a semantic connection. While previous studies employing a repetition-priming paradigm observed largely overlapping networks between semantic and perceptual priming effects, our results suggest that this overlap is only partial (both temporally and spatially). These findings stress the importance of controlling for perceptual features when studying semantic priming.

To what extent electrocorticography (ECoG) and electroencephalography (scalp EEG) differ in their capability to locate sources of deep brain activity is far from evident. Compared to EEG, the spatial resolution and signal-to-noise ratio of ECoG is superior but its spatial coverage is more restricted, as is arguably the volume of tissue activity effectively measured from. Moreover, scalp EEG studies are providing evidence of locating activity from deep sources such as the hippocampus using high-density setups during quiet wakefulness. To address this question, we recorded a multimodal dataset from 4 patients with refractory epilepsy during quiet wakefulness. This data comprises simultaneous scalp, subdural and depth EEG electrode recordings. The latter was located in the hippocampus or insula and provided us with our "ground truth" for source localization of deep activity. We applied independent component analysis (ICA) for the purpose of separating the independent sources in theta, alpha and beta frequency band activity. In all patients subdural- and scalp EEG components were observed which had a significant zero-lag correlation with one or more contacts of the depth electrodes. Subsequent dipole modeling of the correlating components revealed dipole locations that were significantly closer to the depth electrodes compared to the dipole location of non-correlating components. These findings support the idea that components found in both recording modalities originate from neural activity in close proximity to the depth electrodes. Sources localized with subdural electrodes were ~70% closer to the depth electrode than sources localized with EEG with an absolute improvement of around ~2cm. In our opinion, this is not a considerable improvement in source localization accuracy given that, for clinical purposes, ECoG electrodes were implanted in close proximity to the depth electrodes. Furthermore, the ECoG grid attenuates the scalp EEG, due to the electrically isolating silastic sheets in which the ECoG electrodes are embedded. Our results on dipole modeling show that the deep source localization accuracy of scalp EEG is comparable to that of ECoG. SIGNIFICANCE STATEMENT: Deep and subcortical regions play an important role in brain function. However, as joint recordings at multiple spatial scales to study brain function in humans are still scarce, it is still unresolved to what extent ECoG and EEG differ in their capability to locate sources of deep brain activity. To the best of our knowledge, this is the first study presenting a dataset of simultaneously recorded EEG, ECoG and depth electrodes in the hippocampus or insula, with a focus on non-epileptiform activity (quiet wakefulness). Furthermore, we are the first study to provide experimental findings on the comparison of source localization of deep cortical structures between invasive and non-invasive brain activity measured from the cortical surface. ispartof: NEUROIMAGE vol:223 ispartof: location:United States status: published

Contains fulltext : 160981.pdf (Publisher’s version ) (Closed access) Currently, the mechanism of action of vagus nerve stimulation (VNS) is not fully understood, and it is unclear which factors determine a patient's response to treatment. Recent preclinical experiments indicate that activation of the locus coeruleus noradrenergic system is critical for the antiepileptic effect of VNS. This study aims to evaluate the effect of VNS on noradrenergic signaling in the human brain through a noninvasive marker of locus coeruleus noradrenergic activity: the P3 component of the event-related potential. We investigated whether VNS differentially modulates the P3 component in VNS responders versus VNS nonresponders. For this purpose, we recruited 20 patients with refractory epilepsy who had been treated with VNS for at least 18 months. Patients were divided into 2 groups with regard to their reduction in mean monthly seizure frequency: 10 responders (>50 %) and 10 nonresponders (=

In this study, we present long-term results from patients with medial temporal lobe (MTL) epilepsy treated with deep brain stimulation (DBS). Since 2001, 11 patients (8M) with refractory MTL epilepsy underwent MTL DBS. When unilateral DBS failed to decrease seizures by > 90%, a switch to bilateral MTL DBS was proposed. After a mean follow-up of 8.5 years (range: 67–120 months), 6/11 patients had a ≥ 90% seizure frequency reduction with 3/6 seizure-free for > 3 years; three patients had a 40%–70% reduction and two had a < 30% reduction. In 3/5 patients switching to bilateral DBS further improved outcome. Uni- or bilateral MTL DBS did not affect neuropsychological functioning. This open study with an extended long-term follow-up demonstrates maintained efficacy of DBS for MTL epilepsy. In more than half of the patients, a seizure frequency reduction of at least 90% was reached. Bilateral MTL DBS may herald superior efficacy in unilateral MTL epilepsy.

Objective The effects of Deep Brain Stimulation (DBS) have been studied primarily by electrophysiological and neurochemical studies, which lack the ability to elucidate DBS-related responses on a whole-brain scale. With this study our aim is to investigate DBS-induced global neuronal network activation in rats with functional Magnetic Resonance Imaging (fMRI). Methods Three times FMRI was done in seven rats, which were stereotactically implanted with a MR-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Response maps ( p Results Our data indicate that real-time hippocampal DBS evokes a uni- or bilateral BOLD response in hippocampal and mesolimbic structures, depending on the applied stimulation intensity. Results were reproducible in time and in-between subjects. Conclusions We present that DBS-fMRI can be used to detect whole-brain responses to circuit activation with different stimulation intensities, making this technique potentially powerful for exploring DBS-induced cerebral changes for preclinical and clinical DBS. Key message A better understanding of the whole-brain effect of DBS is necessary to improve treatment efficacy in patients. Successful translation of this research to patients might reduce the number of non-responders to this invasive and expensive treatment.

Deep Brain Stimulation (DBS) is a promising treatment for neurological and psychiatric disorders. The mechanism of action and the effects of electrical fields administered to the brain by means of an electrode remain to be elucidated. The effects of DBS have been investigated primarily by electrophysiological and neurochemical studies, which lack the ability to investigate DBS-related responses on a whole-brain scale. Visualization of whole-brain effects of DBS requires functional imaging techniques such as functional Magnetic Resonance Imaging (fMRI), which reflects changes in blood oxygen level dependent (BOLD) responses throughout the entire brain volume. In order to visualize BOLD responses induced by DBS, we have developed an MRI-compatible electrode and an acquisition protocol to perform DBS during BOLD fMRI. In this study, we investigate whether DBS during fMRI is valuable to study local and whole-brain effects of hippocampal DBS and to investigate the changes induced by different stimulation intensities. Seven rats were stereotactically implanted with a custom-made MRI-compatible DBS-electrode in the right hippocampus. High frequency Poisson distributed stimulation was applied using a block-design paradigm. Data were processed by means of Independent Component Analysis. Clusters were considered significant when p-values were