Faculty Bibliography

Recording from neural networks at the resolution of action potentials is critical for understanding how information is processed in the brain. Here, we address this challenge by developing an organic material-based, ultraconformable, biocompatible and scalable neural interface array (the 'NeuroGrid') that can record both local field potentials(LFPs) and action potentials from superficial cortical neurons without penetrating the brain surface. Spikes with features of interneurons and pyramidal cells were simultaneously acquired by multiple neighboring electrodes of the NeuroGrid, allowing for the isolation of putative single neurons in rats. Spiking activity demonstrated consistent phase modulation by ongoing brain oscillations and was stable in recordings exceeding 1 week's duration. We also recorded LFP-modulated spiking activity intraoperatively in patients undergoing epilepsy surgery. The NeuroGrid constitutes an effective method for large-scale, stable recording of neuronal spikes in concert with local population synaptic activity, enhancing comprehension of neural processes across spatiotemporal scales and potentially facilitating diagnosis and therapy for brain disorders.

Historically, the study of speech processing has emphasized a strong link between auditory perceptual input and motor production output. A kind of 'parity' is essential, as both perception- and production-based representations must form a unified interface to facilitate access to higher-order language processes such as syntax and semantics, believed to be computed in the dominant, typically left hemisphere. Although various theories have been proposed to unite perception and production, the underlying neural mechanisms are unclear. Early models of speech and language processing proposed that perceptual processing occurred in the left posterior superior temporal gyrus (Wernicke's area) and motor production processes occurred in the left inferior frontal gyrus (Broca's area). Sensory activity was proposed to link to production activity through connecting fibre tracts, forming the left lateralized speech sensory-motor system. Although recent evidence indicates that speech perception occurs bilaterally, prevailing models maintain that the speech sensory-motor system is left lateralized and facilitates the transformation from sensory-based auditory representations to motor-based production representations. However, evidence for the lateralized computation of sensory-motor speech transformations is indirect and primarily comes from stroke patients that have speech repetition deficits (conduction aphasia) and studies using covert speech and haemodynamic functional imaging. Whether the speech sensory-motor system is lateralized, like higher-order language processes, or bilateral, like speech perception, is controversial. Here we use direct neural recordings in subjects performing sensory-motor tasks involving overt speech production to show that sensory-motor transformations occur bilaterally. We demonstrate that electrodes over bilateral inferior frontal, inferior parietal, superior temporal, premotor and somatosensory cortices exhibit robust sensory-motor neural responses during both perception and production in an overt word-repetition task. Using a non-word transformation task, we show that bilateral sensory-motor responses can perform transformations between speech-perception- and speech-production-based representations. These results establish a bilateral sublexical speech sensory-motor system.

Sensory integration of touch and sight is crucial to perceiving and navigating the environment. While recent evidence from other sensory modality combinations suggests that low-level sensory areas integrate multisensory information at early processing stages, little is known about how the brain combines visual and tactile information. We investigated the dynamics of multisensory integration between vision and touch using the high spatial and temporal resolution of intracranial electrocorticography in humans. We present a novel, two-step metric for defining multisensory integration. The first step compares the sum of the unisensory responses to the bimodal response as multisensory responses. The second step eliminates the possibility that double addition of sensory responses could be misinterpreted as interactions. Using these criteria, averaged local field potentials and high-gamma-band power demonstrate a functional processing cascade whereby sensory integration occurs late, both anatomically and temporally, in the temporo-parieto-occipital junction (TPOJ) and dorsolateral prefrontal cortex. Results further suggest two neurophysiologically distinct and temporally separated integration mechanisms in TPOJ, while providing direct evidence for local suppression as a dominant mechanism for synthesizing visual and tactile input. These results tend to support earlier concepts of multisensory integration as relatively late and centered in tertiary multimodal association cortices.

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!