Responsive Neurostimulation of the Anterior Thalamic Nuclei in Refractory Genetic Generalized Epilepsy: A Case Series.

Genetic generalized epilepsies (GGEs) are thought to represent disorders of thalamocortical networks. There are currently no well-established non-pharmacologic treatment options for patients with drug-resistant GGE. NeuroPace's Responsive Neurostimulation (RNS) System was approved by the United States Food and Drug Administration to treat focal seizures with up to two ictal foci. We report on three adults with drug-resistant GGE who were treated with thalamic RNS. Given the severity of their epilepsies and the potential ictogenic role of the thalamus in the pathophysiology of GGE, the RNS System was palliatively implanted with leads in the bilateral anterior thalamic nuclei (ANT) of these patients. The ANT was selected because it was demonstrated to be a safe target. We retrospectively evaluated metrics including seizure frequency over 18-32 months. One patient required explantation due to infection. The other two patients were clinical responders. By the end of the observation period reported here, one patient was seizure-free for over 9 months. All three self-reported an improved quality of life. The clinical response observed in these patients provides 'proof-of-principle' that GGE may be treatable with responsive thalamic stimulation. Our results support proceeding to a larger study investigating the efficacy and safety of thalamic RNS in drug-resistant GGE.

Prediction of Naming Outcome With fMRI Language Lateralization in Left Temporal Epilepsy Surgery.

BACKGROUND AND OBJECTIVES: Naming decline after left temporal lobe epilepsy (TLE) surgery is common and difficult to predict. Preoperative language fMRI may predict naming decline, but this application is still lacking evidence. We performed a large multicenter cohort study of the effectiveness of fMRI in predicting naming deficits after left TLE surgery. METHODS: At 10 US epilepsy centers, 81 patients with left TLE were prospectively recruited and given the Boston Naming Test (BNT) before and ≈7 months after anterior temporal lobectomy. An fMRI language laterality index (LI) was measured with an auditory semantic decision-tone decision task contrast. Correlations and a multiple regression model were built with a priori chosen predictors. RESULTS: Naming decline occurred in 56% of patients and correlated with fMRI LI (r = -0.41, p < 0.001), age at epilepsy onset (r = -0.30, p = 0.006), age at surgery (r = -0.23, p = 0.039), and years of education (r = 0.24, p = 0.032). Preoperative BNT score and duration of epilepsy were not correlated with naming decline. The regression model explained 31% of the variance, with fMRI contributing 14%, with a 96% sensitivity and 44% specificity for predicting meaningful naming decline. Cross-validation resulted in an average prediction error of 6 points. DISCUSSION: An fMRI-based regression model predicted naming outcome after left TLE surgery in a large, prospective multicenter sample, with fMRI as the strongest predictor. These results provide evidence supporting the use of preoperative language fMRI to predict language outcome in patients undergoing left TLE surgery. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that fMRI language lateralization can help in predicting naming decline after left TLE surgery.

Future of Neurology & Technology: Virtual and Augmented Reality in Neurology and Neuroscience Education: Applications and Curricular Strategies.

Virtual reality and augmented reality have become increasingly prevalent in our lives. They are changing the way we see and interact with the world and have started percolating medical education. In this article, we reviewed key applications of virtual and augmented realities in neurology and neuroscience education, and discussed barriers and opportunities for implementation in the curriculum. Although long-term benefits of these approaches over more traditional learning methods and the optimal curricular balance remain mostly unexplored, virtual and augmented reality can change how we teach neurology and neuroscience.

Temporal lobe regions essential for preserved picture naming after left temporal epilepsy surgery.

OBJECTIVE: To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects. METHODS: Pre- and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug-resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, and the relationship between presence or absence of a lesion and the degree of naming decline was tested at each template voxel while controlling for effects of overall lesion size. RESULTS: Patients declined by an average of 15% in their naming score, with wide variation across individuals. Decline was significantly related to damage in a cluster of voxels in the ventral temporal lobe, located mainly in the fusiform gyrus approximately 4-6 cm posterior to the temporal tip. Extent of damage to this region explained roughly 50% of the variance in outcome. Picture naming decline was not related to hippocampal or temporal pole damage. SIGNIFICANCE: The results provide the first statistical map relating lesion location in left temporal lobe epilepsy surgery to picture naming decline, and they support previous observations of transient naming deficits from electrical stimulation in the basal temporal cortex. The critical lesion is relatively posterior and could be avoided in many patients undergoing left temporal lobe surgery for intractable epilepsy.

Changes in description naming for common and proper nouns after left anterior temporal lobectomy.

Numerous studies have shown that surgical resection of the left anterior temporal lobe (ATL) is associated with a decline in object naming ability (Hermann et al., 1999). In contrast, few studies have examined the effects of left ATL surgery on auditory description naming (ADN) or category-specific naming. Compared with object naming, which loads heavily on visual recognition processes, ADN provides a more specific measure of concept retrieval. The present study examined ADN declines in a large group of patients who were tested before and after left ATL surgery, using a 2 × 2 × 2 factorial manipulation of uniqueness (common vs. proper nouns), taxonomic category (living vs. nonliving things), and time (pre- vs. postsurgery). Significant declines occurred across all categories but were substantially larger for proper living (PL) concepts, i.e., famous individuals. The disproportionate decline in PL noun naming relative to other conditions is consistent with the notion that the left ATL is specialized not only for retrieval of unique entity concepts, but also plays a role in processing social concepts and person-specific features.

Magnetoencephalography in the preoperative evaluation for epilepsy surgery.

People with pharmacoresistant epilepsy are often candidates for resective epilepsy surgery. The presurgical evaluation for epilepsy aims to localize the epileptic network that initiates seizures (which should be disrupted or removed) and determine its spatial relationship to eloquent cortex (which should be preserved). Noninvasive functional imaging techniques play an increasingly important role in planning epilepsy surgery and assessing the feasibility, risks, and benefits of surgery. Magnetoencephalography (MEG) can be a very useful part of a comprehensive presurgical evaluation as it can model the sources of epileptiform activity and localize eloquent cortices within the same study. This review is designed to assist anyone in the field of neurology or related disciplines understand some methods and terminology relevant to clinical MEG. Every effort is made to present the information in nontechnical, approachable ways so that readers will come away with a basic understanding of how to interpret MEG findings when the reported data on one of their patients are presented to them.

Slow cortical dynamics and the accumulation of information over long timescales.

Making sense of the world requires us to process information over multiple timescales. We sought to identify brain regions that accumulate information over short and long timescales and to characterize the distinguishing features of their dynamics. We recorded electrocorticographic (ECoG) signals from individuals watching intact and scrambled movies. Within sensory regions, fluctuations of high-frequency (64-200 Hz) power reliably tracked instantaneous low-level properties of the intact and scrambled movies. Within higher order regions, the power fluctuations were more reliable for the intact movie than the scrambled movie, indicating that these regions accumulate information over relatively long time periods (several seconds or longer). Slow (<0.1 Hz) fluctuations of high-frequency power with time courses locked to the movies were observed throughout the cortex. Slow fluctuations were relatively larger in regions that accumulated information over longer time periods, suggesting a connection between slow neuronal population dynamics and temporally extended information processing.

Widespread Brain Areas Engaged during a Classical Auditory Streaming Task Revealed by Intracranial EEG.

The auditory system must constantly decompose the complex mixture of sound arriving at the ear into perceptually independent streams constituting accurate representations of individual sources in the acoustic environment. How the brain accomplishes this task is not well understood. The present study combined a classic behavioral paradigm with direct cortical recordings from neurosurgical patients with epilepsy in order to further describe the neural correlates of auditory streaming. Participants listened to sequences of pure tones alternating in frequency and indicated whether they heard one or two "streams." The intracranial EEG was simultaneously recorded from sub-dural electrodes placed over temporal, frontal, and parietal cortex. Like healthy subjects, patients heard one stream when the frequency separation between tones was small and two when it was large. Robust evoked-potential correlates of frequency separation were observed over widespread brain areas. Waveform morphology was highly variable across individual electrode sites both within and across gross brain regions. Surprisingly, few evoked-potential correlates of perceptual organization were observed after controlling for physical stimulus differences. The results indicate that the cortical areas engaged during the streaming task are more complex and widespread than has been demonstrated by previous work, and that, by-and-large, correlates of bistability during streaming are probably located on a spatial scale not assessed - or in a brain area not examined - by the present study.