Faculty Bibliography

Rationale: For patients with medically intractable focal epilepsy, the best option for achieving seizure control is often surgical resection. In surgical planning, the potential for seizure reduction must be weighed against the risk of cognitive loss. The role that clinical and demographic factors play in predicting cognitive outcome is well established; however, little is known about the role of crosshemispheric white matter in promoting functional reorganization after surgery. In this study we measured the midsagittal crosssectional area of the corpus callosum (CC) on pre-surgical MRI to investigate whether this property is related to changes in working memory following surgery. Methods: A pre- and post-surgical neuropsychological test battery was obtained in 15 patients (9 males/6 females) who underwent temporal (n = 9), frontal (n = 4), temporal and frontal (n = 1) or parietal lobe (n = 1) resective surgery at NYU Langone Medical Center. Pre-surgical whole-brain T1-weighted 3D MRIs were acquired on all participants from the same dedicated research scanner. The midsaggital CC cross-sectional area was delineated and measured automatically on the MRI using 'yuki' (www.nitrc.org/projects/art), an automatic CC segmentation algorithm, described by Ardekani et al. 2012 (Figure 1A). The Working Memory Index (WMI) from the Wechsler Adult Intelligence Scale was used to probe change in concentration/working memory abilities (postsurgical W

Object Vagus nerve stimulation (VNS) is a viable option for patients with medically intractable epilepsy. However, there are no studies examining its effect on individuals with brain tumor-associated intractable epilepsy. This study aims to evaluate the efficacy of VNS in patients with brain tumor-associated medically intractable epilepsy. Methods Epilepsy surgery databases at 2 separate epilepsy centers were reviewed to identify patients in whom a VNS device was placed for tumor-related intractable epilepsy between January 1999 and December 2011. Preoperative and postoperative seizure frequency and type as well as antiepileptic drug (AED) regimens and degree of tumor progression were evaluated. Statistical analysis was performed using odds ratios and t-tests to examine efficacy. Results Sixteen patients were included in the study. Eight patients (50%) had an improved outcome (Engel Class I, II, or III) with an average follow-up of 39.6 months. The mean reduction in seizure frequency was 41.7% (p = 0.002). There was no significant change in AED regimens. Seizure frequency decreased by 10.9% in patients with progressing tumors and by 65.6% in patients with stable tumors (p = 0.008). Conclusions Vagus nerve stimulation therapy in individuals with brain tumor-associated medically intractable epilepsy was shown to be comparably effective in regard to seizure reduction and response rates to the general population of VNS therapy patients. Outcomes were better in patients with stable as opposed to progressing tumors. The authors' findings support the recommendation of VNS therapy in patients with brain tumor-associated intractable epilepsy, especially in cases in which imminent tumor progression is not expected. Vagus nerve stimulation may not be indicated in more malignant tumors.

Object In this paper the authors' goal was to identify preoperative variables that predict long-term seizure freedom among patients with mesial temporal sclerosis (MTS) after single-stage anterior temporal lobectomy and amygdalohippocampectomy (ATL-AH). Methods The authors retrospectively reviewed 116 consecutive patients (66 females, mean age at surgery 40.7 years) with refractory seizures and pathologically confirmed MTS who underwent ATL-AH with at least 2 years of follow-up. All patients underwent preoperative MRI and video-electroencephalography (EEG); 106 patients (91.4%) underwent Wada testing and 107 patients (92.2%) had neuropsychological evaluations. The authors assessed the concordance of these 4 studies (defined as test consistent with the side of eventual surgery) and analyzed the impact of preoperative variables on seizure freedom. Results The median follow-up after surgery was 6.7 years (mean 6.9 years). Overall, 103 patients (89%) were seizure free, and 109 patients (94%) had Engel Class I or II outcome. Concordant findings were highest for video-EEG (100%), PET (100%), MRI (99.0%), and Wada testing (90.4%) and lowest for SPECT (84.6%) and neuropsychological testing (82.5%). Using binary logistic regression analysis (seizure free or not) and Cox proportional hazard analysis (seizure-free survival), less disparity in the Wada memory scores between the ipsilateral and contralateral sides was associated with persistent seizures. Conclusions Seizure freedom of nearly 90% can be achieved with ATL-AH in properly selected patients with MTS and concordant preoperative studies. The low number of poor outcomes and exclusion of multistage patients limit the statistical power to determine preoperative variables that predict failure. Strong Wada memory lateralization was associated with excellent long-term outcome and adds important localization information to structural and neurophysiological data in predicting outcome after ATL-AH for MTS.

Rationale: Autism spectrum disorders (ASDs), characterized by impaired social interactions, impaired communication and stereotyped behaviors, are highly associated with epilepsy (up to 38%). A shift in cortical excitatory/inhibitory balance towards increased excitation and/or decreased inhibition may play a key role in the pathophysiology of both ASDs and epilepsy. We hypothesized that differences in AMPA receptor (AMPAR) and NMDA receptor (NMDAR) subunit expression in ASD and epilepsy patients may represent a basis for distinct clinical neurological manifestations. Identifying specific synaptic mechanisms for autism and epilepsy will allow development of targeted therapies. Methods: Brain specimens from treatment-resistant temporal lobe epilepsy cases were collected prospectively during resective surgery at NYULMC (n=5; ages 21-37 years). Autopsy temporal and frontal lobe samples from ASD patients (n=5; ages 4-22 years) and regionmatched control specimens from cases with normal neurological history (n=10; ages 5-48 years) were obtained from Maryland Brain and Tissue Bank. All ASD cases met the standard diagnostic criteria (Autism Diagnostic Interview-Revised) and had no evidence of epilepsy, while none of the epilepsy patients were diagnosed with autism. The levels of the NMDAR and AMPAR subunits (NR1, NR2A, NR2B, GluR1 and GluR2) were quantified by Western blot and compared among groups (one-way ANOVA and t-tests). Results: Temporal lobe cortex analysis demonstrated a significant increase in NR1 expression in autism patients (288% of control; p<0.0001), but no significant change in epilepsy cases (96% of control; p>0.05). In both groups, NR2A was significantly decreased (ca. 40% of control; p<0.0001), while NR2B demonstrated a significant upregulation (255% of control in autism and 511% of control in epilepsy; p<0.0001). NR2B levels were significantly higher in epilepsy, relative to autism patients (p<0.001). GluR1 expression was increased in both autism (388% of control; p<0.0001) and epilep!

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.

Intracranial electrode arrays are routinely used in the pre-surgical evaluation of patients with medically refractory epilepsy, and recordings from these electrodes have been increasingly employed in human cognitive neurophysiology due to their high spatial and temporal resolution. For both researchers and clinicians, it is critical to localize electrode positions relative to the subject-specific neuroanatomy. In many centers, a post-implantation MRI is utilized for electrode detection because of its higher sensitivity for surgical complications and the absence of radiation. However, magnetic susceptibility artifacts surrounding each electrode prohibit unambiguous detection of individual electrodes, especially those that are embedded within dense grid arrays. Here, we present an efficient method to accurately localize intracranial electrode arrays based on pre- and post-implantation MR images that incorporates array geometry and the individual's cortical surface. Electrodes are directly visualized relative to the underlying gyral anatomy of the reconstructed cortical surface of individual patients. Validation of this approach shows high spatial accuracy of the localized electrode positions (mean of 0.96mm+/-0.81mm for 271 electrodes across 8 patients). Minimal user input, short processing time, and utilization of radiation-free imaging are strong incentives to incorporate quantitatively accurate localization of intracranial electrode arrays with MRI for research and clinical purposes. Co-registration to a standard brain atlas further allows inter-subject comparisons and relation of intracranial EEG findings to the larger body of neuroimaging literature.

Transmeningeal pharmacotherapy for cerebral cortical disorders requires drug delivery through the subdural/subarachnoid space, ideally with a feedback controlled mechanism. We have developed a device suitable for this function. The first novel component of the apparatus is a silicone rubber strip equipped with (a) fluid-exchange ports for both drug delivery and local cerebrospinal fluid (CSF) removal, and (b) EEG recording electrode contacts. This strip can be positioned between the dura and pia maters. The second novel component is an implantable dual minipump that directs fluid movement to and from the silicone strip and is accessible for refilling and emptying the drug and CSF reservoirs, respectively. This minipump is regulated by a battery-powered microcontroller integrating a bi-directional radiofrequency (RF) communication module. The entire apparatus was implanted in 5 macaque monkeys, with the subdural strip positioned over the frontal cortex and the minipump assembly secured to the cranium under a protective cap. The system was successfully tested for up to 8months for (1) transmeningeal drug delivery using acetylcholine (ACh) and muscimol as test compounds, (2) RF-transmission of neocortical EEG data to assess the efficacy of drug delivery, and (3) local CSF removal for subsequent diagnostic analyses. The device can be used for (a) monitoring neocortical electrophysiology and neurochemistry in freely behaving nonhuman primates for more than 6months, (b) determining the neurobiological impact of subdural/subarachnoid drug delivery interfaces, (c) obtaining novel neuropharmacological data on the effects of central nervous system (CNS) drugs, and (d) performing translational studies to develop subdural pharmacotherapy devices