Faculty Bibliography

Oxytocin is a hypothalamic neuropeptide first recognized as a regulator of parturition and lactation which has recently gained attention for its ability to modulate social behaviors. In this chapter, we review several aspects of the oxytocinergic system, focusing on evidence for release of oxytocin and its receptor distribution in the cortex as the foundation for important networks that control social behavior. We examine the developmental timeline of the cortical oxytocin system as demonstrated by RNA, autoradiographic binding, and protein immunohistochemical studies, and describe how that might shape brain development and behavior. Many recent studies have implicated oxytocin in cognitive processes such as processing of sensory stimuli, social recognition, social memory, and fear. We review these studies and discuss the function of oxytocin in the young and adult cortex as a neuromodulator of central synaptic transmission and mediator of plasticity.

The incidence of oral cancer in the United States is increasing, especially in young people and women. Patients with oral cancer report severe functional pain. Using a patient cohort accrued through the New York University Oral Cancer Center and immune-competent mouse models, we identify a sex difference in the prevalence and severity of oral cancer pain. A neutrophil-mediated endogenous analgesic mechanism is present in male mice with oral cancer. Local naloxone treatment potentiates cancer mediator-induced orofacial nociceptive behavior in male mice only. Tongues from male mice with oral cancer have significantly more infiltrating neutrophils compared to female mice with oral cancer. Neutrophils isolated from the cancer-induced inflammatory microenvironment express beta-endorphin and met-enkephalin. Furthermore, neutrophil depletion results in nociceptive behavior in male mice. These data suggest a role for sex-specific, immune cell-mediated endogenous analgesia in the treatment of oral cancer pain.

The Mal de Debarquement syndrome (MdDS) generally follows sea voyages, but it can occur after turbulent flights or spontaneously. The primary features are objective or perceived continuous rocking, swaying, and/or bobbing at 0.2 Hz after sea voyages or 0.3 Hz after flights. The oscillations can continue for months or years and are immensely disturbing. Associated symptoms appear to be secondary to the incessant sensation of movement. We previously suggested that the illness can be attributed to maladaptation of the velocity storage integrator in the vestibular system, but the actual neural mechanisms driving the MdDS are unknown. Here, based on experiments in subhuman primates, we propose a series of postulates through which the MdDS is generated: (1) The MdDS is produced in the velocity storage integrator by activation of vestibular-only (VO) neurons on either side of the brainstem that are oscillating back and forth at 0.2 or 0.3 Hz. (2) The groups of VO neurons are driven by signals that originate in Purkinje cells in the cerebellar nodulus. (3) Prolonged exposure to roll, either on the sea or in the air, conditions the roll-related neurons in the nodulus. (4) The prolonged exposure causes a shift of the pitch orientation vector from its original position aligned with gravity to a position tilted in roll. (5) Successful treatment involves exposure to a full-field optokinetic stimulus rotating around the spatial vertical countering the direction of the vestibular imbalance. This is done while rolling the head at the frequency of the perceived rocking, swaying, or bobbing. We also note experiments that could be used to verify these postulates, as well as considering potential flaws in the logic. Important unanswered questions: (1) Why does the MdDS predominantly affect women? (2) What aspect of roll causes the prolongation of the tilted orientation vector, and why is it so prolonged in some individuals? (3) What produces the increase in symptoms of some patients when returning home after treatment, and how can this be avoided? We also posit that the same mechanisms underlie the less troublesome and shorter duration Mal de Debarquement.

OBJECTIVE:To assess bimodal auditory performance in children with a cochlear implant (CI) and contralateral auditory brainstem implant (ABI). METHODS:This is a retrospective case review performed at a tertiary referral center. Four patients with cochlear nerve deficiency initially underwent cochlear implantation but were not benefiting from their devices and underwent ABI in the contralateral ear. The main outcome measures included age-appropriate speech perception and production assessments. RESULTS:Three subjects performed better on their auditory perception assessments using both of their devices than with either device alone. One subject had only preliminary outcomes, but subjectively performed best with both devices. CONCLUSIONS:We observed continued improvement in CI performance over time, even if no benefit was evident before the decision for ABI. This could suggest that ABI and CI have a synergistic effect, or it could simply be the adaptive ability of the developing brain to utilize the signals coming from these devices. There is preliminary evidence to support choosing the ear contralateral to the CI for an ABI in a pediatric patient with bilateral cochlear nerve deficiency.

Purpose: Prior studies have shown correlation between relative cerebral blood volume (rCBV) and patient survival and tumor genomics. The purpose of this study was to determine whether rCBV values correlate with isocitrate dehydrogenase (IDH) mutation status, genome-wide CNV (copy number variation) and patient overall survival in diffuse gliomas. Materials & Methods: 107 treatment naive gliomas (62 patients from TCGA/TCIA dataset and 45 patients from our institute) (44 glioblastoma and 63 lower grade gliomas) with DSC T2* perfusion data were included. IDH mutation and survival data were assayed by the TCGA, and pre-surgical imaging collected by The Cancer Imaging Archive. CNVabundance plots obtained with Illumina 850k EPIC DNA methylation arrays were reviewed in 19 patients. The association of rCBV with tumor genomics, CNV and overall survival were analyzed. Results: IDH-wildtype gliomas (44.8%) demonstrated higher rCBV values (rCBV = 6.87 +/- 3.09) than IDH-mutated gliomas (55.2%, rCBV =2.21 +/- 1.71 for 1p/19q codeleted gliomas and 2.09 +/- 2.00 for non-codeleted gliomas, ANOVA, p<0.0001). rCBV is a significant predictor of overall survival (HR 1.23, p<0.0001). Gliomas with rCBV < 3.80 showed better survival (n = 54, median survival time unobserved) than gliomas with rCBV > 3.8 (n = 53, median 18 months; log-rank p<0.0001). IDHwt gliomas with high rCBV had the worst survival (10.6% surviving at 3 years, 95% CI (4%, 30%)). CNV-S IDHmut 1p19q noncodeleted gliomas demonstrated significantly lower mean rCBV (1.4 +/- 0.4) than CNV-U gliomas (4.0 +/- 1.1, p = 0.009). Conclusion: IDHwt gliomas show higher rCBV than IDHmut gliomas irrespective of the glioma grade. Higher rCBV measurements are associated with poorer survival in the entire cohort and also within IDHmut and IDHwt gliomas. IDHmut 1p19q noncodeleted gliomas with higher CNV abundance (CNV-U) also show higher CBV when compared with those with lesser degree of CNVabundance (CNV-S)