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Department/Unit:Otolaryngology

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Functional Segregation of Cortical Regions Underlying Speech Timing and Articulation

Long, Michael A; Katlowitz, Kalman A; Svirsky, Mario A; Clary, Rachel C; Byun, Tara McAllister; Majaj, Najib; Oya, Hiroyuki; Howard, Matthew A 3rd; Greenlee, Jeremy D W
Spoken language is a central part of our everyday lives, but the precise roles that individual cortical regions play in the production of speech are often poorly understood. To address this issue, we focally lowered the temperature of distinct cortical regions in awake neurosurgical patients, and we relate this perturbation to changes in produced speech sequences. Using this method, we confirm that speech is highly lateralized, with the vast majority of behavioral effects seen on the left hemisphere. We then use this approach to demonstrate a clear functional dissociation between nearby cortical speech sites. Focal cooling of pars triangularis/pars opercularis (Broca's region) and the ventral portion of the precentral gyrus (speech motor cortex) resulted in the manipulation of speech timing and articulation, respectively. Our results support a class of models that have proposed distinct processing centers underlying motor sequencing and execution for speech.
PMCID:4833207
PMID: 26924439
ISSN: 1097-4199
CID: 2009232

New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

Sturm, Dominik; Orr, Brent A; Toprak, Umut H; Hovestadt, Volker; Jones, David T W; Capper, David; Sill, Martin; Buchhalter, Ivo; Northcott, Paul A; Leis, Irina; Ryzhova, Marina; Koelsche, Christian; Pfaff, Elke; Allen, Sariah J; Balasubramanian, Gnanaprakash; Worst, Barbara C; Pajtler, Kristian W; Brabetz, Sebastian; Johann, Pascal D; Sahm, Felix; Reimand, Juri; Mackay, Alan; Carvalho, Diana M; Remke, Marc; Phillips, Joanna J; Perry, Arie; Cowdrey, Cynthia; Drissi, Rachid; Fouladi, Maryam; Giangaspero, Felice; Lastowska, Maria; Grajkowska, Wieslawa; Scheurlen, Wolfram; Pietsch, Torsten; Hagel, Christian; Gojo, Johannes; Lotsch, Daniela; Berger, Walter; Slavc, Irene; Haberler, Christine; Jouvet, Anne; Holm, Stefan; Hofer, Silvia; Prinz, Marco; Keohane, Catherine; Fried, Iris; Mawrin, Christian; Scheie, David; Mobley, Bret C; Schniederjan, Matthew J; Santi, Mariarita; Buccoliero, Anna M; Dahiya, Sonika; Kramm, Christof M; von Bueren, Andre O; von Hoff, Katja; Rutkowski, Stefan; Herold-Mende, Christel; Fruhwald, Michael C; Milde, Till; Hasselblatt, Martin; Wesseling, Pieter; Rossler, Jochen; Schuller, Ulrich; Ebinger, Martin; Schittenhelm, Jens; Frank, Stephan; Grobholz, Rainer; Vajtai, Istvan; Hans, Volkmar; Schneppenheim, Reinhard; Zitterbart, Karel; Collins, V Peter; Aronica, Eleonora; Varlet, Pascale; Puget, Stephanie; Dufour, Christelle; Grill, Jacques; Figarella-Branger, Dominique; Wolter, Marietta; Schuhmann, Martin U; Shalaby, Tarek; Grotzer, Michael; van Meter, Timothy; Monoranu, Camelia-Maria; Felsberg, Jorg; Reifenberger, Guido; Snuderl, Matija; Forrester, Lynn Ann; Koster, Jan; Versteeg, Rogier; Volckmann, Richard; van Sluis, Peter; Wolf, Stephan; Mikkelsen, Tom; Gajjar, Amar; Aldape, Kenneth; Moore, Andrew S; Taylor, Michael D; Jones, Chris; Jabado, Nada; Karajannis, Matthias A; Eils, Roland; Schlesner, Matthias; Lichter, Peter; von Deimling, Andreas; Pfister, Stefan M; Ellison, David W; Korshunov, Andrey; Kool, Marcel
Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are highly aggressive, poorly differentiated embryonal tumors occurring predominantly in young children but also affecting adolescents and adults. Herein, we demonstrate that a significant proportion of institutionally diagnosed CNS-PNETs display molecular profiles indistinguishable from those of various other well-defined CNS tumor entities, facilitating diagnosis and appropriate therapy for patients with these tumors. From the remaining fraction of CNS-PNETs, we identify four new CNS tumor entities, each associated with a recurrent genetic alteration and distinct histopathological and clinical features. These new molecular entities, designated "CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2)," "CNS Ewing sarcoma family tumor with CIC alteration (CNS EFT-CIC)," "CNS high-grade neuroepithelial tumor with MN1 alteration (CNS HGNET-MN1)," and "CNS high-grade neuroepithelial tumor with BCOR alteration (CNS HGNET-BCOR)," will enable meaningful clinical trials and the development of therapeutic strategies for patients affected by poorly differentiated CNS tumors.
PMCID:5139621
PMID: 26919435
ISSN: 1097-4172
CID: 1965622

A Distributed Network for Social Cognition Enriched for Oxytocin Receptors

Mitre, Mariela; Marlin, Bianca J; Schiavo, Jennifer K; Morina, Egzona; Norden, Samantha E; Hackett, Troy A; Aoki, Chiye J; Chao, Moses V; Froemke, Robert C
Oxytocin is a neuropeptide important for social behaviors such as maternal care and parent-infant bonding. It is believed that oxytocin receptor signaling in the brain is critical for these behaviors, but it is unknown precisely when and where oxytocin receptors are expressed or which neural circuits are directly sensitive to oxytocin. To overcome this challenge, we generated specific antibodies to the mouse oxytocin receptor and examined receptor expression throughout the brain. We identified a distributed network of female mouse brain regions for maternal behaviors that are especially enriched for oxytocin receptors, including the piriform cortex, the left auditory cortex, and CA2 of the hippocampus. Electron microscopic analysis of the cerebral cortex revealed that oxytocin receptors were mainly expressed at synapses, as well as on axons and glial processes. Functionally, oxytocin transiently reduced synaptic inhibition in multiple brain regions and enabled long-term synaptic plasticity in the auditory cortex. Thus modulation of inhibition may be a general mechanism by which oxytocin can act throughout the brain to regulate parental behaviors and social cognition. SIGNIFICANCE STATEMENT: Oxytocin is an important peptide hormone involved in maternal behavior and social cognition, but it has been unclear what elements of neural circuits express oxytocin receptors due to the paucity of suitable antibodies. Here, we developed new antibodies to the mouse oxytocin receptor. Oxytocin receptors were found in discrete brain regions and at cortical synapses for modulating excitatory-inhibitory balance and plasticity. These antibodies should be useful for future studies of oxytocin and social behavior.
PMCID:4764667
PMID: 26911697
ISSN: 1529-2401
CID: 1964812

Effective Modulation of Male Aggression through Lateral Septum to Medial Hypothalamus Projection

Wong, Li Chin; Wang, Li; D'Amour, James A; Yumita, Tomohiro; Chen, Genghe; Yamaguchi, Takashi; Chang, Brian C; Bernstein, Hannah; You, Xuedi; Feng, James E; Froemke, Robert C; Lin, Dayu
Aggression is a prevalent behavior in the animal kingdom that is used to settle competition for limited resources. Given the high risk associated with fighting, the central nervous system has evolved an active mechanism to modulate its expression. Lesioning the lateral septum (LS) is known to cause "septal rage," a phenotype characterized by a dramatic increase in the frequency of attacks. To understand the circuit mechanism of LS-mediated modulation of aggression, we examined the influence of LS input on the cells in and around the ventrolateral part of the ventromedial hypothalamus (VMHvl)-a region required for male mouse aggression. We found that the inputs from the LS inhibited the attack-excited cells but surprisingly increased the overall activity of attack-inhibited cells. Furthermore, optogenetic activation of the projection from LS cells to the VMHvl terminated ongoing attacks immediately but had little effect on mounting. Thus, LS projection to the ventromedial hypothalamic area represents an effective pathway for suppressing male aggression.
PMCID:4783202
PMID: 26877081
ISSN: 1879-0445
CID: 1949592

Evolution of surgical techniques for mandibular reconstruction using free fibula flaps: The next generation

Monaco, Casian; Stranix, John T; Avraham, Tomer; Brecht, Lawrence; Saadeh, Pierre B; Hirsch, David; Levine, Jamie P
BACKGROUND: Virtual surgical planning (VSP) has contributed to a number of technical innovations in mandible reconstruction. We report on these innovations and the overall evolution of mandible reconstruction using free fibula flaps at our institution. METHODS: We performed a retrospective chart review of all patients who underwent virtually planned free fibula flap reconstruction of the mandible. Comparisons were made between cohorts based on distinct eras related to the virtual planning approach. RESULTS: Seventy-six patients underwent a total of 78 VSP-assisted mandible reconstructions with free fibula flaps. Significant differences were noted among the groups with regard to mean number of segments, percentage of flaps that had at least 3 segments, percentage of flaps that had double-barrel components, and innovations per flap. CONCLUSION: VSP-assisted mandible reconstruction has contributed to more complex surgeries at our institution. The technology ensures functional restoration, permitting an optimized aesthetic reconstruction that has not increased operative times or complications. (c) 2016 Wiley Periodicals, Inc. Head Neck, 2016.
PMID: 26876700
ISSN: 1097-0347
CID: 1949572

The onset of visual experience gates auditory cortex critical periods

Mowery, Todd M; Kotak, Vibhakar C; Sanes, Dan H
Sensory systems influence one another during development and deprivation can lead to cross-modal plasticity. As auditory function begins before vision, we investigate the effect of manipulating visual experience during auditory cortex critical periods (CPs) by assessing the influence of early, normal and delayed eyelid opening on hearing loss-induced changes to membrane and inhibitory synaptic properties. Early eyelid opening closes the auditory cortex CPs precociously and dark rearing prevents this effect. In contrast, delayed eyelid opening extends the auditory cortex CPs by several additional days. The CP for recovery from hearing loss is also closed prematurely by early eyelid opening and extended by delayed eyelid opening. Furthermore, when coupled with transient hearing loss that animals normally fully recover from, very early visual experience leads to inhibitory deficits that persist into adulthood. Finally, we demonstrate a functional projection from the visual to auditory cortex that could mediate these effects.
PMCID:4736048
PMID: 26786281
ISSN: 2041-1723
CID: 1942132

Predictors of Altered Upper Extremity Function During the First Year After Breast Cancer Treatment

Smoot, Betty; Paul, Steven M; Aouizerat, Bradley E; Dunn, Laura; Elboim, Charles; Schmidt, Brian; Hamolsky, Deborah; Levine, Jon D; Abrams, Gary; Mastick, Judy; Topp, Kimberly; Miaskowski, Christine
OBJECTIVE: The purpose of this study was to evaluate trajectories of and predictors for changes in upper extremity (UE) function in women (n = 396) during the first year after breast cancer treatment. DESIGN: Prospective, longitudinal assessments of shoulder range of motion (ROM), grip strength, and perceived interference of function were performed before and for 1 year after surgery. Demographic, clinical, and treatment characteristics were evaluated as predictors of postoperative function. RESULTS: Women had a mean (SD) age of 54.9 (11.6) years, and 64% were white. Small but statistically significant reductions in shoulder ROM were found on the affected side over 12 months (P < 0.001). Predictors of interindividual differences in ROM at the 1-month assessment were ethnicity, neoadjuvant chemotherapy, type of surgery, axillary lymph node dissection, and preoperative ROM. Predictors of interindividual differences in changes over time in postoperative ROM were living alone, type of surgery, axillary lymph node dissection, and adjuvant chemotherapy. Declines in mean grip strength from before through 1 month after surgery were small and not clinically meaningful. Women with greater preoperative breast pain interference scores had higher postoperative interference scores at all postoperative assessments. CONCLUSION: Some of the modifiable risk factors identified in this study can be targeted for intervention to improve UE function in these women.
PMCID:4967035
PMID: 26829093
ISSN: 1537-7385
CID: 1933422

The neural encoding of formant frequencies contributing to vowel identification in normal-hearing listeners

Won, Jong Ho; Tremblay, Kelly; Clinard, Christopher G; Wright, Richard A; Sagi, Elad; Svirsky, Mario
Even though speech signals trigger coding in the cochlea to convey speech information to the central auditory structures, little is known about the neural mechanisms involved in such processes. The purpose of this study was to understand the encoding of formant cues and how it relates to vowel recognition in listeners. Neural representations of formants may differ across listeners; however, it was hypothesized that neural patterns could still predict vowel recognition. To test the hypothesis, the frequency-following response (FFR) and vowel recognition were obtained from 38 normal-hearing listeners using four different vowels, allowing direct comparisons between behavioral and neural data in the same individuals. FFR was employed because it provides an objective and physiological measure of neural activity that can reflect formant encoding. A mathematical model was used to describe vowel confusion patterns based on the neural responses to vowel formant cues. The major findings were (1) there were large variations in the accuracy of vowel formant encoding across listeners as indexed by the FFR, (2) these variations were systematically related to vowel recognition performance, and (3) the mathematical model of vowel identification was successful in predicting good vs poor vowel identification performers based exclusively on physiological data.
PMCID:4706540
PMID: 26826999
ISSN: 1520-8524
CID: 1931872

Cochlear Implantation in the Setting of Cochlear Ossification as Sequela of Malarial Meningitis

Svrakic, Maja; Rafii, Benjamin; Roland, J Thomas Jr
PMID: 25118582
ISSN: 1537-4505
CID: 1930872

Significance of Intravenous Thrombus in the Management of Adrenocortical Carcinoma: Prognosis and Surgical Implications [Meeting Abstract]

Ahmed, S; Tran, T; Levine, EA; Weber, S; Salem, AI; Postlewait, LM; Maithel, SK; Wang, T; Hatzaras, I; Shenoy, R; Phay, J; Shirley, L; Fields, RC; Jin, L; Pawlik, TM; Prescott, J; Sicklick, J; Gad, S; Yopp, A; Mansour, J; Duh, Q; Seiser, N; Solorzano, CC; Kiernan, CM; Poultsides, GA; Votanopoulos, K
ISI:000368185000272
ISSN: 1534-4681
CID: 1930822