Dr. Ramayya is an assistant professor in the Department of Neurosurgery. He specializes in the treatment of patients with chronic pain, movement disorders, epilepsy, and traumatic brain injury. His research program will focus on understanding brain mechanisms underlying pain experience and how to alleviate pain using brain stimulation.

Dr. Ramayya specializes in neuromodulation, including deep brain stimulation (DBS), spinal cord stimulation, MRI-guided laser therapy, and focused ultrasound. Dr. Ramayya obtained his MD and PhD from the University of Pennsylvania, where he also completed his neurosurgery residency and a fellowship in stereotactic and functional neurosurgery.

His research efforts have identified neural substrates underlying learning, memory, and decision-making using computational behavioral modeling, neurophysiology, and neuroimaging.

Dr. Ramayya has published in numerous peer-reviewed journals, including the Journal of Neuroscience, NeuroImage, and Cerebral Cortex. He has also presented his work at national and international meetings, including those for the American Association of Neurological Surgeons and the Pan Philadelphia Neurosurgery Conference.

Clinical Focus

  • Neurological Surgery

Academic Appointments

Honors & Awards

  • Neurosurgery Resident Research Presentation Award, Pan Philadelphia
  • Dorothea Jameson and Leo M. Hurvich Travel Award, Perelman School of Medicine
  • Medical Scientist Training Program Scholarship, National Institutes of Health

Professional Education

  • Fellowship: Pennsylvania Hospital PA
  • Residency: Hospital of the University of Pennsylvania (2023) PA
  • Medical Education: Perelman School of Medicine University of Pennsylvania (2016) PA

2023-24 Courses

All Publications

  • Dichotomous frequency-dependent phase synchrony in the sensorimotor network characterizes simplistic movement. Scientific reports Buch, V. P., Brandon, C., Ramayya, A. G., Lucas, T. H., Richardson, A. G. 2024; 14 (1): 11933


    It is hypothesized that disparate brain regions interact via synchronous activity to control behavior. The nature of these interconnected ensembles remains an area of active investigation, and particularly the role of high frequency synchronous activity in simplistic behavior is not well known. Using intracranial electroencephalography, we explored the spectral dynamics and network connectivity of sensorimotor cortical activity during a simple motor task in seven epilepsy patients. Confirming prior work, we see a "spectral tilt" (increased high-frequency (HF, 70-100 Hz) and decreased low-frequency (LF, 3-33 Hz) broadband oscillatory activity) in motor regions during movement compared to rest, as well as an increase in LF synchrony between these regions using time-resolved phase-locking. We then explored this phenomenon in high frequency and found a robust but opposite effect, where time-resolved HF broadband phase-locking significantly decreased during movement. This "connectivity tilt" (increased LF synchrony and decreased HF synchrony) displayed a graded anatomical dependency, with the most robust pattern occurring in primary sensorimotor cortical interactions and less robust pattern occurring in associative cortical interactions. Connectivity in theta (3-7 Hz) and high beta (23-27 Hz) range had the most prominent low frequency contribution during movement, with theta synchrony building gradually while high beta having the most prominent effect immediately following the cue. There was a relatively sharp, opposite transition point in both the spectral and connectivity tilt at approximately 35 Hz. These findings support the hypothesis that task-relevant high-frequency spectral activity is stochastic and that the decrease in high-frequency synchrony may facilitate enhanced low frequency phase coupling and interregional communication. Thus, the "connectivity tilt" may characterize behaviorally meaningful cortical interactions.

    View details for DOI 10.1038/s41598-024-62848-9

    View details for PubMedID 38789576

    View details for PubMedCentralID 2868968

  • Naturalistic acute pain states decoded from neural and facial dynamics. bioRxiv : the preprint server for biology Huang, Y., Gopal, J., Kakusa, B., Li, A. H., Huang, W., Wang, J. B., Persad, A., Ramayya, A., Parvizi, J., Buch, V. P., Keller, C. 2024


    Pain is a complex experience that remains largely unexplored in naturalistic contexts, hindering our understanding of its neurobehavioral representation in ecologically valid settings. To address this, we employed a multimodal, data-driven approach integrating intracranial electroencephalography, pain self-reports, and facial expression quantification to characterize the neural and behavioral correlates of naturalistic acute pain in twelve epilepsy patients undergoing continuous monitoring with neural and audiovisual recordings. High self-reported pain states were associated with elevated blood pressure, increased pain medication use, and distinct facial muscle activations. Using machine learning, we successfully decoded individual participants' high versus low self-reported pain states from distributed neural activity patterns (mean AUC = 0.70), involving mesolimbic regions, striatum, and temporoparietal cortex. High self-reported pain states exhibited increased low-frequency activity in temporoparietal areas and decreased high-frequency activity in mesolimbic regions (hippocampus, cingulate, and orbitofrontal cortex) compared to low pain states. This neural pain representation remained stable for hours and was modulated by pain onset and relief. Objective facial expression changes also classified self-reported pain states, with results concordant with electrophysiological predictions. Importantly, we identified transient periods of momentary pain as a distinct naturalistic acute pain measure, which could be reliably differentiated from affect-neutral periods using intracranial and facial features, albeit with neural and facial patterns distinct from self-reported pain. These findings reveal reliable neurobehavioral markers of naturalistic acute pain across contexts and timescales, underscoring the potential for developing personalized pain interventions in real-world settings.

    View details for DOI 10.1101/2024.05.10.593652

    View details for PubMedID 38766098

    View details for PubMedCentralID PMC11100805

  • Ethical Issues in Intraoperative Neuroscience Research: Assessing Subjects' Recall of Informed Consent and Motivations for Participation. AJOB empirical bioethics Wexler, A., Choi, R. J., Ramayya, A. G., Sharma, N., McShane, B. J., Buch, L. Y., Donley-Fletcher, M. P., Gold, J. I., Baltuch, G. H., Goering, S., Klein, E. 2022; 13 (1): 57-66


    BackgroundAn increasing number of studies utilize intracranial electrophysiology in human subjects to advance basic neuroscience knowledge. However, the use of neurosurgical patients as human research subjects raises important ethical considerations, particularly regarding informed consent and undue influence, as well as subjects' motivations for participation. Yet a thorough empirical examination of these issues in a participant population has been lacking. The present study therefore aimed to empirically investigate ethical concerns regarding informed consent and voluntariness in Parkinson's disease patients undergoing deep brain stimulator (DBS) placement who participated in an intraoperative neuroscience study.MethodsTwo semi-structured 30-minute interviews were conducted preoperatively and postoperatively via telephone. Interviews assessed participants' motivations for participation in the parent intraoperative study, recall of information presented during the informed consent process, and participants' postoperative reflections on the research study.ResultsTwenty-two participants (mean age = 60.9) completed preoperative interviews at a mean of 7.8 days following informed consent and a mean of 5.2 days prior to DBS surgery. Twenty participants completed postoperative interviews at a mean of 5 weeks following surgery. All participants cited altruism or advancing medical science as "very important" or "important" in their decision to participate in the study. Only 22.7% (n = 5) correctly recalled one of the two risks of the study. Correct recall of other aspects of the informed consent was poor (36.4% for study purpose; 50.0% for study protocol; 36.4% for study benefits). All correctly understood that the study would not confer a direct therapeutic benefit to them.ConclusionEven though research coordinators were properly trained and the informed consent was administered according to protocol, participants demonstrated poor retention of study information. While intraoperative studies that aim to advance neuroscience knowledge represent a unique opportunity to gain fundamental scientific knowledge, improved standards for the informed consent process can help facilitate their ethical implementation.

    View details for DOI 10.1080/23294515.2021.1941415

    View details for PubMedID 34227925

    View details for PubMedCentralID PMC9188847

  • Tractography-Based Surgical Targeting for Thalamic Deep Brain Stimulation: A Comparison of Probabilistic vs Deterministic Fiber Tracking of the Dentato-Rubro-Thalamic Tract. Neurosurgery Yang, A. I., Parker, D., Vijayakumari, A. A., Ramayya, A. G., Donley-Fletcher, M. P., Aunapu, D., Wolf, R. L., Baltuch, G. H., Verma, R. 2022; 90 (4): 419-425


    The ventral intermediate (VIM) thalamic nucleus is the main target for the surgical treatment of refractory tremor. Initial targeting traditionally relies on atlas-based stereotactic targeting formulas, which only minimally account for individual anatomy. Alternative approaches have been proposed, including direct targeting of the dentato-rubro-thalamic tract (DRTT), which, in clinical settings, is generally reconstructed with deterministic tracking. Whether more advanced probabilistic techniques are feasible on clinical-grade magnetic resonance acquisitions and lead to enhanced reconstructions is poorly understood.To compare DRTT reconstructed with deterministic vs probabilistic tracking.This is a retrospective study of 19 patients with essential tremor who underwent deep brain stimulation (DBS) with intraoperative neurophysiology and stimulation testing. We assessed the proximity of the DRTT to the DBS lead and to the active contact chosen based on clinical response.In the commissural plane, the deterministic DRTT was anterior (P < 10-4) and lateral (P < 10-4) to the DBS lead. By contrast, although the probabilistic DRTT was also anterior to the lead (P < 10-4), there was no difference in the mediolateral dimension (P = .5). Moreover, the 3-dimensional Euclidean distance from the active contact to the probabilistic DRTT was smaller vs the distance to the deterministic DRTT (3.32 ± 1.70 mm vs 5.01 ± 2.12 mm; P < 10-4).DRTT reconstructed with probabilistic fiber tracking was superior in spatial proximity to the physiology-guided DBS lead and to the empirically chosen active contact. These data inform strategies for surgical targeting of the VIM.

    View details for DOI 10.1227/NEU.0000000000001840

    View details for PubMedID 35044356

    View details for PubMedCentralID PMC9514748

  • Anticipatory influences on simple sensory-motor behaviors are encoded by rapidly fluctuating neural dynamics across the human brain Ramayya , A., Buch , V., Richardson , A., Lucas , T., Gold , J. bioRxiv. 2022



  • Social Determinants of Health and Neurosurgical Outcomes: Current State and Future Directions. Neurosurgery Glauser, G., Detchou, D. K., Dimentberg, R., Ramayya, A. G., Malhotra, N. R. 2021; 88 (5): E383-E390


    The relationship between social determinants of health (SDOH) and neurosurgical outcomes has become increasingly relevant. To date, results of prior work evaluating the impact of social determinants in neurosurgery have been mixed, and the need for robust data on this subject remains. The present review evaluates how gender, race, and socioeconomic status (SES) influence outcomes following various brain tumor resection procedures. Results from a number of prior studies from the senior author's lab are summarized, with all data acquired using the EpiLog tool (Epilog Laser). Separate analyses were performed for each procedure, evaluating the unique, isolated impact of gender, race, and SES on outcomes. A comprehensive literature review identified any prior studies evaluating the influence of these SDOH on neurosurgical outcomes. The review presented herein suggests that the effect of gender and race on outcomes is largely mitigated when equal access to care is attained, and socioeconomic factors and comorbidities are controlled for. Furthermore, when patients are matched upon for a number of clinically relevant covariates, SES impacts postoperative mortality. Elucidation of this disparity empowers surgeons to initiate actionable change to equilibrate future outcomes.

    View details for DOI 10.1093/neuros/nyab030

    View details for PubMedID 33677591

  • Thoracolumbar Transverse Process Fractures Are More Frequently Associated with Nonspinal Injury than Clinically Significant Spine Fracture. World neurosurgery Arena, J. D., Kvint, S., Ghenbot, Y., Howard, S., Ramayya, A. G., Sinha, S., Petrov, D., Chen, H. I., Schuster, J. M. 2021; 146: e1236-e1241


    We studied the risk of associated spinal and nonspinal injuries (NSIs) in the setting of observed thoracolumbar transverse process fracture (TPF) and examined the clinical management of TPF.Patients treated at a Level I trauma center over a 5-year period were screened for thoracolumbar TPF. Prevalence of associated spinal fractures and NSIs as well as relationship to level of TPF was explored. Clinical management and follow-up outcomes were reviewed.A total of 252 patients with thoracolumbar TPFs were identified. NSIs were commonly observed (70.6%, n = 178); however, associated spinal fractures were more rarely seen (24.6%, n = 62, P < 0.0001). No patients had neurological deficits attributable to TPFs, and only 3 patients with isolated TPFs were treated with orthosis. Among patients with outpatient follow-up (70.6%, n = 178), none developed delayed-onset neurological deficits or spinal instability. Thoracic TPFs (odds ratio = 3.56, 95% confidence interval = 1.20-10.56) and L1 TPFs (odds ratio = 2.48, 95% confidence interval = 1.41-4.36) were predictive of associated thoracic NSIs. L5 TPF was associated with pelvic fractures (odds ratio = 6.30, 95% confidence interval = 3.26-12.17). There was no difference in rate of NSIs between isolated TPF (70.0%) and TPF with associated clinically relevant spinal fracture (72.6%, P = 0.70).NSIs are nearly 3 times more common in patients with thoracolumbar TPFs than associated clinically relevant spinal fractures. Spine service consultation for TPF may be unnecessary unless fracture is associated with a clinically relevant spinal injury, which represents a minority of cases. However, detection of TPF should raise suspicion for high likelihood of associated NSIs.

    View details for DOI 10.1016/j.wneu.2020.11.129

    View details for PubMedID 33271381

  • Theta Synchrony Is Increased near Neural Populations That Are Active When Initiating Instructed Movement ENEURO Ramayya, A. G., Yang, A., Buch, V. P., Burke, J. F., Richardson, A. G., Brandon, C., Stein, J. M., Davis, K. A., Chen, H., Proekt, A., Kelz, M. B., Litt, B., Gold, J., Lucas, T. H. 2021; 8 (1)


    Theta oscillations (3-8 Hz) in the human brain have been linked to perception, cognitive control, and spatial memory, but their relation to the motor system is less clear. We tested the hypothesis that theta oscillations coordinate distributed behaviorally relevant neural representations during movement using intracranial electroencephalography (iEEG) recordings from nine patients (n = 490 electrodes) as they performed a simple instructed movement task. Using high frequency activity (HFA; 70-200 Hz) as a marker of local spiking activity, we identified electrodes that were positioned near neural populations that showed increased activity during instruction and movement. We found that theta synchrony was widespread throughout the brain but was increased near regions that showed movement-related increases in neural activity. These results support the view that theta oscillations represent a general property of brain activity that may also play a specific role in coordinating widespread neural activity when initiating voluntary movement.

    View details for DOI 10.1523/ENEURO.0252-20.2020

    View details for Web of Science ID 000641651800015

    View details for PubMedID 33355232

    View details for PubMedCentralID PMC7901148

  • Surface-Registration Frameless Stereotactic Navigation Is Less Accurate During Prone Surgeries: Intraoperative Near-Infrared Visualization Using Second Window Indocyanine Green Offers an Adjunct. Molecular imaging and biology Cho, S. S., Teng, C. W., Ramayya, A., Buch, L., Hussain, J., Harsch, J., Brem, S., Lee, J. Y. 2020; 22 (6): 1572-1580


    Frameless neuronavigation allows neurosurgeons to visualize and relate the position of surgical instruments to intracranial pathologies based on preoperative tomographic imaging. However, neuronavigation can often be inaccurate. Multiple factors have been proposed as potential causes, and new technologies are needed to overcome these challenges.To evaluate the accuracy of neuronavigation systems compared to near-infrared (NIR) fluorescence imaging using Second Window Indocyanine Green, a novel technique, and to determine factors that lead to neuronavigation errors.A retrospective analysis was conducted on 56 patients who underwent primary resections of intracranial tumors. Patients received 5 mg/kg ICG approximately 24 h preoperatively. Intraoperatively, neuronavigation was used to plan craniotomies to place the tumors in the center. After craniotomy, NIR imaging visualized tumor-specific NIR signals. The accuracy of neuronavigation and NIR fluorescence imaging for delineating the tumor boundary prior to durotomy was compared.The neuronavigation centers and NIR centers were 23.0 ± 7.7 % and 2.6 ± 1.1 % deviated from the tumor centers, respectively, relative to the craniotomy sizes. In 12 cases, significant changes were made to the planned durotomy based on NIR imaging. Patient position was a significant predictor of neuronavigation inaccuracy on both univariate and multivariate analysis, with the prone position having significantly higher inaccuracy (29.2 ± 8.1 %) compared to the supine (16.2 ± 8.1 %, p value < 0.001) or the lateral (17.9 ± 5.1 %, p value = 0.003) positions.Patient position significantly affects neuronavigation accuracy. Intraoperative NIR fluorescence imaging before durotomy offers an opportunity to readjust the neuronavigation image space to better align with the patient space.

    View details for DOI 10.1007/s11307-020-01495-8

    View details for PubMedID 32232627

    View details for PubMedCentralID 3563325

  • Focused Ultrasound Thalamotomy with Dentato-Rubro-Thalamic Tractography in Patients with Spinal Cord Stimulators and Cardiac Pacemakers STEREOTACTIC AND FUNCTIONAL NEUROSURGERY Buch, V. P., McShane, B. J., Beatson, N., Yang, A., Blanke, A., Tilden, D., Korn, M., Chaibainou, H., Ramayya, A., Wombacher, K., Maier, S., Marashlian, T., Wolf, R., Baltuch, G. H. 2020; 98 (4): 263-269


    Magnetic resonance image-guided high-intensity focused ultrasound (MRgFUS)-based thermal ablation of the ventral intermediate nucleus of the thalamus (VIM) is a minimally invasive treatment modality for essential tremor (ET). Dentato-rubro-thalamic tractography (DRTT) is becoming increasingly popular for direct targeting of the presumed VIM ablation focus. It is currently unclear if patients with implanted pulse generators (IPGs) can safely undergo MRgFUS ablation and reliably acquire DRTT suitable for direct targeting. We present an 80-year-old male with a spinal cord stimulator (SCS) and an 88-year-old male with a cardiac pacemaker who both underwent MRgFUS for medically refractory ET. Clinical outcomes were measured using the Clinical Rating Scale for Tremor (CRST). DRTT was successfully created and imaging parameter adjustments did not result in any delay in procedural time in either case. In the first case, 7 therapeutic sonications were delivered. The patient improved immediately and durably with a 90% CRST-disability improvement at 6-week follow-up. In our second case, 6 therapeutic sonications were delivered with durable, 75% CRST-disability improvement at 6 weeks. These are the first cases of MRgFUS thalamotomy in patients with IPGs. DRTT targeting and MRgFUS-based thermal ablation can be safely performed in these patients using a 1.5-T MRI.

    View details for DOI 10.1159/000507031

    View details for Web of Science ID 000605966100006

    View details for PubMedID 32403106

  • Thalamic Deep Brain Stimulation for Essential Tremor: Relation of the Dentatorubrothalamic Tract with Stimulation Parameters WORLD NEUROSURGERY Yang, A., Buch, V. P., Heman-Ackah, S. M., Ramayya, A. G., Hitti, F. L., Beatson, N., Chaibainou, H., Yates, M., Wang, S., Verma, R., Wolf, R. L., Baltuch, G. H. 2020; 137: E89-E97


    In deep brain stimulation (DBS) for essential tremor, the primary target ventrointermedius (VIM) nucleus cannot be clearly visualized with structural imaging. As such, there has been much interest in the dentatorubrothalamic tract (DRTT) for target localization, but evidence for the DRTT as a putative stimulation target in tremor suppression is lacking. We evaluated proximity of the DRTT in relation to DBS stimulation parameters.This is a retrospective analysis of 26 consecutive patients who underwent DBS with microelectrode recordings (46 leads). Fiber tracking was performed with a published deterministic technique. Clinically optimized stimulation parameters were obtained in all patients at the time of most recent follow-up (6.2 months). Volume of tissue activated (VTA) around contacts was calculated from a published model.Tremor severity was reduced in all treated hemispheres, with 70% improvement in the treated hand score of the Clinical Rating Scale for Tremor. At the level of the active contact (2.9 ± 2.0 mm superior to the commissural plane), the center of the DRTT was lateral to the contacts (5.1 ± 2.1 mm). The nearest fibers of the DRTT were 2.4 ± 1.7 mm from the contacts, whereas the radius of the VTA was 2.9 ± 0.7 mm. The VTA overlapped with the DRTT in 77% of active contacts. The distance from active contact to the DRTT was positively correlated with stimulation voltage requirements (Kendall τ = 0.33, P = 0.006), whereas distance to the atlas-based VIM coordinates was not.Active contacts in proximity to the DRTT had lower voltage requirements. Data from a large cohort provide support for the DRTT as an effective stimulation target for tremor control.

    View details for Web of Science ID 000532762900003

    View details for PubMedID 31954907

    View details for PubMedCentralID PMC7584387

  • Association of spinal instability due to metastatic disease with increased mortality and a proposed clinical pathway for treatment. Journal of neurosurgery. Spine Sullivan, P. Z., Albayar, A., Ramayya, A. G., McShane, B., Marcotte, P., Malhotra, N. R., Ali, Z. S., Chen, H. I., Janjua, M. B., Saifi, C., Schuster, J., Grady, M. S., Jones, J., Ozturk, A. K. 2020: 1-8


    Multidisciplinary treatment including medical oncology, radiation oncology, and surgical consultation is necessary to provide comprehensive therapy for patients with spinal metastases. The goal of this study was to review the use of radiation therapy and/or surgical intervention and their impact on patient outcomes.In this retrospective series, the authors identified at their institution those patients with spinal metastases who had received radiation therapy alone or had undergone surgery with or without radiation therapy within a 6-year period. Data on patient age, chemotherapy, surgical procedure, radiation therapy, Karnofsky Performance Status (KPS), primary tumor pathology, Spinal Instability Neoplastic Score (SINS), and survival after treatment were collected from the patient electronic medical records. N - 1 chi-square testing was used for comparisons of proportions. The Student t-test was used for comparisons of means. A p value < 0.05 was considered statistically significant. A survival analysis was completed using a multivariate Cox proportional hazards model.Two hundred thirty patients with spinal metastases were identified, 109 of whom had undergone surgery with or without radiation therapy. Among the 104 patients for whom the surgical details were reviewed, 34 (33%) had a history of preoperative radiation to the surgical site but ultimately required surgical intervention. In this surgical group, a significantly increased frequency of death within 30 days was noted for the SINS unstable patients (23.5%) as compared to that for the SINS stable patients (2.3%; p < 0.001). The SINS was a significant predictor of time to death among surgical patients (HR 1.11, p = 0.037). Preoperative KPS was not independently associated with decreased survival (p > 0.5) on univariate analysis. One hundred twenty-six patients met the criteria for inclusion in the radiation-only analysis. Ninety-eight of these patients (78%) met the criteria for potential instability (PI) at the time of treatment, according to the SINS system. Five patients (5%) with PI in the radiation therapy group had a documented neurosurgical or orthopedic surgery consultation prior to radiation therapy.At the authors' institution, patients with gross mechanical instability per the SINS system had an increased rate of 30-day postoperative mortality, which remained significant when controlling for other factors. Surgical consultation for metastatic spine patients receiving radiation oncology consultation with PI is low. The authors describe an institutional pathway to encourage multidisciplinary treatment from the initial encounter in the emergency department to expedite surgical evaluation and collaboration.

    View details for DOI 10.3171/2019.11.SPINE19775

    View details for PubMedID 32059185

  • Single neurons throughout human memory regions phase-lock to hippocampal theta Schonhaut , D., Ramayya , A., Solomon , E., Herweg , N., Fried , I., Kahana , M. bioRxiv. 2020
  • Association of Overlapping Neurosurgery With Patient Outcomes at a Large Academic Medical Center. Neurosurgery Agarwal, P., Ramayya, A. G., Osiemo, B., Goodrich, S., Glauser, G., McClintock, S. D., Chen, H. I., Schuster, J. M., Grady, M. S., Malhotra, N. R. 2019; 85 (6): E1050-E1058


    Limited data exist on the safety of overlapping surgery, a practice that has recently received widespread attention.To examine the association of overlapping neurosurgery with patient outcomes.A total of 3038 routinely scheduled, elective neurosurgical procedures were retrospectively reviewed at a single, multihospital academic medical center. Procedures were categorized into any overlap or no overlap and further subcategorized into beginning overlap (first 50% of procedure only), end overlap (last 50% of procedure only), and middle overlap (overlap at the midpoint).A total of 1030 (33.9%) procedures had any overlap, whereas 278 (9.2%) had beginning overlap, 190 (6.3%) had end overlap, and 476 (15.7%) had middle overlap. Compared with no overlap patients, patients with any overlap had lower American Society of Anesthesiologists scores (P = .0018), less prior surgery (P < .0001), and less prior neurosurgery (P < .0001), though they tended to be older (P < .0001) and more likely in-patients (P = .0038). Any-overlap patients had decreased overall mortality (2.8% vs 4.5%; P = .025), 30- to 90-d readmission rate (3.1% vs 5.5%; P = .0034), 30- to 90-d reoperation rate (1.0% vs 2.0%; P = .03), 30- to 90-d emergency room (ER) visit rate (2.1% vs 3.7%; P = .018), and future surgery on index admission (2.8% vs 7.3%; P < .0001). Multiple regression analysis validated noninferior outcomes for overlapping surgery, except for the association of increased future surgery on index admission with middle overlap (odds ratio 3.99; 95% confidence interval [1.91, 8.33]).Overlapping neurosurgery is associated with noninferior patient outcomes that may be driven by surgeon selection of healthier patients, regardless of specific overlap timing.

    View details for DOI 10.1093/neuros/nyz243

    View details for PubMedID 31432069

  • Association of Surgical Overlap during Wound Closure with Patient Outcomes among Neurological Surgery Patients at a Large Academic Medical Center. Neurosurgery Glauser, G., Agarwal, P., Ramayya, A. G., Chen, H. I., Lee, J. Y., Schuster, J. M., Osiemo, B., Goodrich, S., Smith, L. J., McClintock, S. D., Malhotra, N. R. 2019; 85 (5): E882-E888


    Several studies have explored the effect of overlapping surgery on patient outcomes, but impact of surgical overlap during wound closure has not been studied.To examine the association of overlap during wound closure and suture time overlap (STO) with patient outcomes in a heterogeneous neurosurgical population.Over 4 yr (7/2013-7/2017), 1 7689 neurosurgical procedures were retrospectively reviewed at a single, multihospital academic medical center. STO was defined as all surgeries for which an overlapping surgery occurred, exclusively, during wound closure of the index case being studied. We excluded nonelective cases and overlapping surgeries that involved overlap during surgical portions of the case other than wound closure. Tests of independence and Wilcoxon tests were used for statistical analysis.Patients with STO had a shortened length of hospital stay (100.6 vs 135.1 h; P < .0001), reduced deaths in follow-up (1.59% vs 5.45%; P = .0004), and lower 30- to 90-d readmission rates (3.64% vs 7.47%; P = .0026). Patients with STO had no increase in revision surgery. Patients with STO had longer wound closure times (26.5 vs 23.9 min; P < .0001) but shorter total surgical times (nonclosure surgical time 101.8 vs 133.3 min; P < .0001; and total surgical time 128.3 vs 157.1 min; P < .0001).Surgical overlap during wound closure (STO) is associated with improved or at least noninferior patient outcomes, as it pertains to readmissions and wound revisions.

    View details for DOI 10.1093/neuros/nyz142

    View details for PubMedID 31058970

  • Assessing the utility of an IoS application in the perioperative care of spine surgery patients: the NeuroPath Pilot study. mHealth Glauser, G., Ali, Z. S., Gardiner, D., Ramayya, A. G., Pessoa, R., Grady, M. S., Welch, W. C., Zager, E. L., Sim, E., Haughey, V., Wells, B., Restuccia, M., Tait, G., Fala, G., Malhotra, N. R. 2019; 5: 40


    In an attempt to improve care while decreasing costs and postoperative pain, we developed a novel IoS mobile health application, NeuroPath. The objective of this innovative app is to integrate enhanced recovery after surgery (ERAS) principles, patient education, and real-time pain and activity monitoring in a home setting with unencumbered two-way communication.The NeuroPath application was built over 18 months, with support from Apple, Medable, the Department of Information-Technology and the Department of Neurosurgery. Target areas addressed by NeuroPath include patient prep for surgery, perioperative risk mitigation, activity monitoring, wound care, and opioid use management. These target areas are monitored through a provider app, which is downloaded to the care providers IPad Mini. The provider app permits real time viewing of wound healing (patient incision photographs), activity levels, pain levels, and narcotic usage. Participants are given a daily To-Do list, via the Care Card section of the interface. The To-Do list presents the patient with specific tasks for exercise, instructions to wash incision area, pre-operative instructions, directions for discussing medication with care team, among other patient specific recommendations.Of the 30 patients enrolled in the pilot study, there was a range of activity on the app. Patients with high involvement in the app logged in nearly every day from a week pre-op to >45 days post-op. Data for patients that utilized the app and uploaded regularly show trends of appropriately healing wounds, decreasing levels of pain, increasing step counts, and discontinuation of narcotics.This pilot study of the NeuroPath app demonstrates its potential utility for improving quality of patient care without increased costs. Participants who regularly used the app showed consistent improvement throughout the post-operative recovery period (increasing ambulation, decreasing pain and guided reduction in narcotic usage).

    View details for DOI 10.21037/mhealth.2019.09.01

    View details for PubMedID 31620467

    View details for PubMedCentralID PMC6789206

  • Surgical Management of Idiopathic Thoracic Spinal Cord Herniation. World neurosurgery Neale, N., Ramayya, A., Welch, W. 2019; 129: 81-84


    Idiopathic spinal cord herniation is a rare condition that involves spinal cord herniation through a defect in the ventral dura.We present a case of a 61-year-old woman who initially presented in 2016 with an approximately 1-year history of burning right lower extremity pain and gait instability. Her neurologic examination was consistent with thoracic Brown-Sequard syndrome, and spinal magnetic resonance imaging showed a focal defect in the ventral dura at the superior aspect of T4 with the left aspect of the cord herniating into the defect. In 2018, she underwent a T3-T4 laminectomy with T3 pedicle take down and medial facetectomy, with reduction of the herniated cord.Idiopathic spinal cord herniation is an uncommon spinal cord disorder with a paucity of data reported. Our case report of a classic case of idiopathic spinal cord herniation presenting as Brown-Sequard syndrome and managed surgically will contribute to the data in this field.

    View details for DOI 10.1016/j.wneu.2019.05.219

    View details for PubMedID 31158530

  • Assessing variability in surgical decision making among attending neurosurgeons at an academic center. Journal of neurosurgery Ramayya, A. G., Chen, H. I., Marcotte, P. J., Brem, S., Zager, E. L., Osiemo, B., Piazza, M., Sharma, N., McClintock, S. D., Schuster, J. M., Ali, Z. S., Connolly, P., Heuer, G. G., Grady, M. S., Kung, D. K., Ozturk, A. K., O'Rourke, D. M., Malhotra, N. R. 2019; 132 (6): 1970-1976


    Although it is known that intersurgeon variability in offering elective surgery can have major consequences for patient morbidity and healthcare spending, data addressing variability within neurosurgery are scarce. The authors performed a prospective peer review study of randomly selected neurosurgery cases in order to assess the extent of consensus regarding the decision to offer elective surgery among attending neurosurgeons across one large academic institution.All consecutive patients who had undergone standard inpatient surgical interventions of 1 of 4 types (craniotomy for tumor [CFT], nonacute redo CFT, first-time spine surgery with/without instrumentation, and nonacute redo spine surgery with/without instrumentation) during the period 2015-2017 were retrospectively enrolled (n = 9156 patient surgeries, n = 80 randomly selected individual cases, n = 20 index cases of each type randomly selected for review). The selected cases were scored by attending neurosurgeons using a need for surgery (NFS) score based on clinical data (patient demographics, preoperative notes, radiology reports, and operative notes; n = 616 independent case reviews). Attending neurosurgeon reviewers were blinded as to performing provider and surgical outcome. Aggregate NFS scores across various categories were measured. The authors employed a repeated-measures mixed ANOVA model with autoregressive variance structure to compute omnibus statistical tests across the various surgery types. Interrater reliability (IRR) was measured using Cohen's kappa based on binary NFS scores.Overall, the authors found that most of the neurosurgical procedures studied were rated as "indicated" by blinded attending neurosurgeons (mean NFS = 88.3, all p values < 0.001) with greater agreement among neurosurgeon raters than expected by chance (IRR = 81.78%, p = 0.016). Redo surgery had lower NFS scores and IRR scores than first-time surgery, both for craniotomy and spine surgery (ANOVA, all p values < 0.01). Spine surgeries with fusion had lower NFS scores than spine surgeries without fusion procedures (p < 0.01).There was general agreement among neurosurgeons in terms of indication for surgery; however, revision surgery of all types and spine surgery with fusion procedures had the lowest amount of decision consensus. These results should guide efforts aimed at reducing unnecessary variability in surgical practice with the goal of effective allocation of healthcare resources to advance the value paradigm in neurosurgery.

    View details for DOI 10.3171/2019.2.JNS182658

    View details for PubMedID 31151100

  • Factors Predicting Ventriculostomy Revision at a Large Academic Medical Center WORLD NEUROSURGERY Ramayya, A. G., Glauser, G., Mcshane, B., Branche, M., Sinha, S., Kvint, S., Buch, V., Abdullah, K. G., Kung, D., Chen, H., Malhotra, N. R., Ozturk, A. 2019; 123: E509-E514


    Freehand bedside ventriculostomy placement can result in catheter malfunction requiring a revision procedure and cause significant patient morbidity. We performed a single-center retrospective review to assess factors related to this complication.Using an administrative database and chart review, we identified 101 first-time external ventricular drain placements performed at the bedside. We collected data regarding demographics, medical comorbidities, complications, and catheter tip location. We performed univariate and multivariate statistical analyses using MATLAB. We corrected for multiple comparisons using the false discovery rate (FDR) procedure.Multivariate regression analyses revealed that revision procedures were more likely to occur after drain blockage (odds ratio [OR] 17.9) and hemorrhage (OR 10.3, FDR-corrected P values < 0.01, 0.05, respectively). Drain blockage was less frequent after placement in an "optimal location" (ipsilateral ventricle or near foramen of Monroe; OR 0.09, P = 0.009, FDR-corrected P < 0.03) but was more likely to occur after placement in third ventricle (post-hoc P values < 0.015). Primary diagnoses included subarachnoid hemorrhage (n = 30, 29.7%), intraparenchymal hemorrhage with intraventricular extravasation (n = 24, 23.7%), tumor (n = 20, 19.8%), and trauma (n = 17, 16.8%). Most common complications included drain blockage (n = 12, 11.8%) and hemorrhage (n = 8, 7.9%). In total, 16 patients underwent at least 1 revision procedure (15.8%).Bedside external ventricular drain placement is associated with a 15% rate of revision, that typically occurred after drain blockage and postprocedure hemorrhage. Optimal placement within the ipsilateral frontal horn or foramen of Monroe was associated with a reduced rate of drain blockage.

    View details for DOI 10.1016/j.wneu.2018.11.196

    View details for Web of Science ID 000462958400059

    View details for PubMedID 30503293

  • Long-term outcomes following deep brain stimulation for Parkinson's disease. Journal of neurosurgery Hitti, F. L., Ramayya, A. G., McShane, B. J., Yang, A. I., Vaughan, K. A., Baltuch, G. H. 2019: 1-6


    OBJECTIVE: Deep brain stimulation (DBS) is an effective treatment for several movement disorders, including Parkinson's disease (PD). While this treatment has been available for decades, studies on long-term patient outcomes have been limited. Here, the authors examined survival and long-term outcomes of PD patients treated with DBS. METHODS: The authors conducted a retrospective analysis using medical records of their patients to identify the first 400 consecutive patients who underwent DBS implantation at their institution from 1999 to 2007. The medical record was used to obtain baseline demographics and neurological status. The authors performed survival analyses using Kaplan-Meier estimation and multivariate regression using Cox proportional hazards modeling. Telephone surveys were used to determine long-term outcomes. RESULTS: Demographics for the cohort of patients with PD (n = 320) were as follows: mean age of 61 years, 70% male, 27% of patients had at least 1 medical comorbidity (coronary artery disease, congestive heart failure, diabetes mellitus, atrial fibrillation, or deep vein thrombosis). Kaplan-Meier survival analysis on a subset of patients with at least 10 years of follow-up (n = 200) revealed a survival probability of 51% (mean age at death 73 years). Using multivariate regression, the authors found that age at implantation (HR 1.02, p = 0.01) and male sex (HR 1.42, p = 0.02) were predictive of reduced survival. Number of medical comorbidities was not significantly associated with survival (p > 0.5). Telephone surveys were completed by 40 surviving patients (mean age 55.1 ± 6.4 years, 72.5% male, 95% subthalamic nucleus DBS, mean follow-up 13.0 ± 1.7 years). Tremor responded best to DBS (72.5% of patients improved), while other motor symptoms remained stable. Ability to conduct activities of daily living (ADLs) remained stable (dressing, 78% of patients; running errands, 52.5% of patients) or worsened (preparing meals, 50% of patients). Patient satisfaction, however, remained high (92.5% happy with DBS, 95% would recommend DBS, and 75% felt it provided symptom control). CONCLUSIONS: DBS for PD is associated with a 10-year survival rate of 51%. Survey data suggest that while DBS does not halt disease progression in PD, it provides durable symptomatic relief and allows many individuals to maintain ADLs over long-term follow-up greater than 10 years. Furthermore, patient satisfaction with DBS remains high at long-term follow-up.

    View details for DOI 10.3171/2018.8.JNS182081

    View details for PubMedID 30660117

  • Epilepsy: Temporal Lobectomy with Invasive Monitoring Functional Neurosurgery: The Essentials. Ramayya, A., Baltuch, . 2019
  • Globus Pallidus Interna Deep Brain Stimulation: Practical Guide to Placement with Microelectrode Recording Surgery for Parkinson's Disease Hudgins, E., Baltuch, A. 2019
  • Reduced long-term cost and increased patient satisfaction with rechargeable implantable pulse generators for deep brain stimulation. Journal of neurosurgery Hitti, F. L., Vaughan, K. A., Ramayya, A. G., McShane, B. J., Baltuch, G. H. 2018; 131 (3): 799-806


    Deep brain stimulation (DBS) has revolutionized the treatment of neurological disease, but its therapeutic efficacy is limited by the lifetime of the implantable pulse generator (IPG) batteries. At the end of the battery life, IPG replacement surgery is required. New IPGs with rechargeable batteries (RC-IPGs) have recently been introduced and allow for decreased reoperation rates for IPG replacements. The authors aimed to examine the merits and limitations of these devices.The authors reviewed the medical records of patients who underwent DBS implantation at their institution. RC-IPGs were placed either during initial DBS implantation or during an IPG change. A cost analysis was performed that compared RC-IPGs with standard IPGs, and telephone patient surveys were conducted to assess patient satisfaction.The authors identified 206 consecutive patients from 2011 to 2016 who underwent RC-IPG placement (mean age 61 years; 67 women, 33%). Parkinson's disease was the most common indication for DBS (n = 144, 70%), followed by essential tremor (n = 41, 20%), dystonia (n = 13, 6%), depression (n = 5, 2%), multiple sclerosis tremor (n = 2, 1%), and epilepsy (n = 1, 0.5%). DBS leads were typically placed bilaterally (n = 192, 93%) and targeted the subthalamic nucleus (n = 136, 66%), ventral intermediate nucleus of the thalamus (n = 43, 21%), internal globus pallidus (n = 21, 10%), ventral striatum (n = 5, 2%), or anterior nucleus of the thalamus (n = 1, 0.5%). RC-IPGs were inserted at initial DBS implantation in 123 patients (60%), while 83 patients (40%) were converted to RC-IPGs during an IPG replacement surgery. The authors found that RC-IPG implantation resulted in $60,900 of cost savings over the course of 9 years. Furthermore, patient satisfaction was high with RC-IPG implantation. Overall, 87.3% of patients who responded to the survey were satisfied with their device, and only 6.7% found the rechargeable component difficult to use. In patients who were switched from a standard IPG to RC-IPG, the majority who responded (70.3%) preferred the rechargeable IPG.RC-IPGs can provide DBS patients with long-term therapeutic benefit while minimizing the need for battery replacement surgery. The authors have implanted rechargeable stimulators in 206 patients undergoing DBS surgery, and here they demonstrate the cost-effectiveness and high patient satisfaction associated with this procedure.

    View details for DOI 10.3171/2018.4.JNS172995

    View details for PubMedID 30265199

  • Neurologic Status on Presentation as Predictive Measurement in Success of Closed Reduction in Traumatic Cervical Facet Fractures. World neurosurgery Branche, M. J., Ozturk, A. K., Ramayya, A. G., McShane, B. J., Schuster, J. M. 2018; 114: e344-e349


    Dislocations to cervical facets resulting from traumatic injury often lead to neurologic impairment and can be treated both surgically and in a closed manner.We sought to evaluate the utilization of closed reduction in the initial management of bilateral facet dislocations over the past 10 years at our institution.We retrospectively reviewed the charts of patients who experienced subaxial cervical facet injury within the Penn Health System between 1 June 2006 and 1 June 2016 to identify patients with bilateral jumped/perched facets. The neurologic injury was identified on the basis of the American Spinal Injury Association (ASIA) spinal cord injury score. Analysis of variance and 2-sample t-tests were used to compare continuous distributions, and chi-square tests were used to compare categorical distributions.We focused our analyses on patients who presented with bilateral jumped/perched facets with (ASIA A and B) or without (ASIA C, D, E) complete voluntary motor deficit and underwent attempted closed reduction. We found that the rate of successful closed reduction was significantly higher in incomplete motor deficits (5/5, P = 0.04, chi-square test) as compared with complete motor deficits (n = 2/11).Our results demonstrate a significant difference in the success rate of closed reduction in patients with good neurologic status on presentation (ASIA A or B), compared with those with poor neurologic status (ASIA C, D, and E). These results suggest that closed reduction should be attempted in patients with good motor examinations on presentation, whereas those with significant deficits may benefit from earlier surgical intervention.

    View details for DOI 10.1016/j.wneu.2018.03.001

    View details for PubMedID 29530687

  • A Retrospective Propensity Score-Matched Early Thromboembolic Event Analysis of Prothrombin Complex Concentrate vs Fresh Frozen Plasma for Warfarin Reversal Prior to Emergency Neurosurgical Procedures. Neurosurgery Agarwal, P., Abdullah, K. G., Ramayya, A. G., Nayak, N. R., Lucas, T. H. 2018; 82 (6): 877-886


    Reversal of therapeutic anticoagulation prior to emergency neurosurgical procedures is required in the setting of intracranial hemorrhage. Multifactor prothrombin complex concentrate (PCC) promises rapid efficacy but may increase the probability of thrombotic complications compared to fresh frozen plasma (FFP).To compare the rate of thrombotic complications in patients treated with PCC or FFP to reverse therapeutic anticoagulation prior to emergency neurosurgical procedures in the setting of intracranial hemorrhage at a level I trauma center.Sixty-three consecutive patients on warfarin therapy presenting with intracranial hemorrhage who received anticoagulation reversal prior to emergency neurosurgical procedures were retrospectively identified between 2007 and 2016. They were divided into 2 cohorts based on reversal agent, either PCC (n = 28) or FFP (n = 35). The thrombotic complications rates within 72 h of reversal were compared using the χ2 test. A multivariate propensity score matching analysis was used to limit the threat to interval validity from selection bias arising from differences in demographics, laboratory values, history, and clinical status.Thrombotic complications were uncommon in this neurosurgical population, occurring in 1.59% (1/63) of treated patients. There was no significant difference in the thrombotic complication rate between groups, 3.57% (1/28; PCC group) vs 0% (0/35; FFP group). Propensity score matching analysis validated this finding after controlling for any selection bias.In this limited sample, thrombotic complication rates were similar between use of PCC and FFP for anticoagulation reversal in the management of intracranial hemorrhage prior to emergency neurosurgical procedures.

    View details for DOI 10.1093/neuros/nyx327

    View details for PubMedID 29106685

  • Posterior Cervical Laminectomy Results in Better Radiographic Decompression of Spinal Cord Compared with Anterior Cervical Discectomy and Fusion. World neurosurgery Piazza, M., McShane, B. J., Ramayya, A. G., Sullivan, P. Z., Ali, Z. S., Marcotte, P. J., Welch, W. C., Ozturk, A. K. 2018; 110: e362-e366


    Cervical spondylitic myelopathy is a degenerative condition resulting from chronic spinal cord compression and a leading cause of nontraumatic spinal cord dysfunction. The chief surgical goal in the management of cervical spondylitic myelopathy is adequate spinal cord decompression with or without fusion to slow or prevent further neurologic decline. We conducted a radiographic analysis of canal parameters preoperatively and postoperatively for patients undergoing either anterior or posterior cervical decompression.Preoperative and postoperative radiographic analysis was performed using midsagittal and axial magnetic resonance imaging at the level of the disc space for 37 patients who underwent anterior or posterior cervical decompression. Statistical comparisons between anterior and posterior groups were performed using independent t test and Mann-Whitney U test where appropriate.Both postoperative anteroposterior canal diameter and posterior cerebrospinal fluid (CSF) space were greater in patients undergoing posterior decompression (P = 0.011 and P < 0.001, respectively), although postoperative anterior CSF space was comparable between both groups. Both anterior and posterior approaches to decompression resulted in a statistically significant improvement in anteroposterior diameter, anterior CSF space, and posterior CSF space (P < 0.001). Posterior decompression yielded significantly greater change in anteroposterior diameter and posterior CSF space compared with the anterior approach (P < 0.001).In this quantitative radiographic study, we found that although both posterior cervical laminectomy and anterior cervical discectomy yielded significant decompression, laminectomy yielded a greater degree of decompression of the posterior CSF space.

    View details for DOI 10.1016/j.wneu.2017.11.017

    View details for PubMedID 29138070

  • Stimulation of the human medial temporal lobe between learning and recall selectively enhances forgetting. Brain stimulation Merkow, M. B., Burke, J. F., Ramayya, A. G., Sharan, A. D., Sperling, M. R., Kahana, M. J. 2017; 10 (3): 645-650


    Direct electrical stimulation applied to the human medial temporal lobe (MTL) typically disrupts performance on memory tasks, however, the mechanism underlying this effect is not known.To study the effects of MTL stimulation on memory performance.We studied the effects of MTL stimulation on memory in five patients undergoing invasive electrocorticographic monitoring during various phases of a memory task (encoding, distractor, recall).We found that MTL stimulation disrupted memory performance in a timing-dependent manner; we observed greater forgetting when applying stimulation during the delay between encoding and recall, compared to when it was applied during encoding or recall.The results suggest that recall is most dependent on the MTL between learning and retrieval.

    View details for DOI 10.1016/j.brs.2016.12.011

    View details for PubMedID 28073638

    View details for PubMedCentralID PMC5410394

  • Thirty-Day Readmission Rates Following Deep Brain Stimulation Surgery. Neurosurgery Ramayya, A. G., Abdullah, K. G., Mallela, A. N., Pierce, J. T., Thawani, J., Petrov, D., Baltuch, G. H. 2017; 81 (2): 259-267


    Deep brain stimulation (DBS) has emerged as a safe and efficacious surgical intervention for several movement disorders; however, the 30-day all-cause readmission rate associated with this procedure has not previously been documented.To perform a retrospective cohort study to estimate the 30-day all-cause readmission rate associated with DBS.We reviewed medical records of patients over the age of 18 who underwent DBS surgery at Pennsylvania Hospital of the University of Pennsylvania between 2009 and 2014. We identified patients who were readmitted to an inpatient medical facility within 30 days from their initial discharge.Over the study period, 23 (6.6%) of 347 DBS procedures resulted in a readmission to the hospital within 30 days. Causes of readmission were broadly categorized into surgery-related (3.7%): intracranial lead infection (0.6%), battery-site infection (0.6%), intracranial hematoma along the electrode tract (0.6%), battery-site hematoma (0.9%), and seizures (1.2%); and nonsurgery-related (2.9%): altered mental status (1.8%), nonsurgical-site infections (0.6%), malnutrition and poor wound healing (0.3%), and a pulse generator malfunction requiring reprogramming (0.3%). Readmissions could be predicted by the presence of medical comorbidities ( P < .001), but not by age, gender, or length of stay ( P s > .15).All-cause 30-day readmission for DBS is 6.6%. This compares favorably to previously studied neurosurgical procedures. Readmissions frequently resulted from surgery-related complications, particularly infection, seizures, and hematomas, and were significantly associated with the presence of medical comorbidities ( P < .001).

    View details for DOI 10.1093/neuros/nyx019

    View details for PubMedID 28327899

  • Proximity of Substantia Nigra Microstimulation to Putative GABAergic Neurons Predicts Modulation of Human Reinforcement Learning. Frontiers in human neuroscience Ramayya, A. G., Pedisich, I., Levy, D., Lyalenko, A., Wanda, P., Rizzuto, D., Baltuch, G. H., Kahana, M. J. 2017; 11: 200


    Neuronal firing in the substantia nigra (SN) immediately following reward is thought to play a crucial role in human reinforcement learning. As in Ramayya et al. (2014a) we applied microstimulation in the SN of patients undergoing deep brain stimulation (DBS) for the treatment of Parkinson's disease as they engaged in a two-alternative reinforcement learning task. We obtained microelectrode recordings to assess the proximity of the electrode tip to putative dopaminergic and GABAergic SN neurons and applied stimulation to assess the functional importance of these neuronal populations for learning. We found that the proximity of SN microstimulation to putative GABAergic neurons predicted the degree of stimulation-related changes in learning. These results extend previous work by supporting a specific role for SN GABA firing in reinforcement learning. Stimulation near these neurons appears to dampen the reinforcing effect of rewarding stimuli.

    View details for DOI 10.3389/fnhum.2017.00200

    View details for PubMedID 28536513

    View details for PubMedCentralID PMC5422436

  • Operative Strategies to Minimize Complications Following Resection of Pituitary Macroadenomas. Journal of neurological surgery. Part B, Skull base Thawani, J. P., Ramayya, A. G., Pisapia, J. M., Abdullah, K. G., Lee, J. Y., Grady, M. S. 2017; 78 (2): 184-190


    Introduction We sought to identify factors associated with increased length of stay (LOS) and morbidity in patients undergoing resection of pituitary macroadenomas. Methods We reviewed records of 203 consecutive patients who underwent endoscopic endonasal resection of a pituitary macroadenoma (mean age = 55.7 [16-88]) years, volume = 11.3 (1.0-134.3) cm3. Complete resection was possible in 60/29.6% patients. Mean follow-up was 575 days. Multivariate logistic regression was performed using MATLAB. Results Mean LOS was 4.67 (1-66) days and was associated with CSF leak (p = 0.025), lumbar drain placement (p = 0.041; n = 8/3.9% intraoperative, n = 20/9.9% postoperative), and any infection (p = 0.066). Age, diabetes insipidus (n = 17/8.37%), and syndrome of inappropriate antidiuretic hormone secretion (n = 12/5.9%) were not associated with increased LOS (p > 0.2). Postoperative CSF leak in the hospital (n = 21/10.3%) was associated with intraoperative CSF leak (p = 0.002; n = 82/40.4%) and complete resection (p = 0.012). There was no significant association (p > 0.1) between postoperative CSF leak in the hospital following surgery and the use of a fat graft (n = 61/30.1%), nasoseptal flap (155/76.4%), or perioperative lumbar drain placement (n = 8/3.94%). Conclusion Complete resection is associated with increased risk of CSF leak and LOS. Operative strategies including placement of fat graft, nasoseptal flap, or intraoperative lumbar drain placement may have limited value in reducing the risk of postoperative CSF leak.

    View details for DOI 10.1055/s-0036-1597276

    View details for PubMedID 28321384

    View details for PubMedCentralID PMC5357219

  • Resident simulation training in endoscopic endonasal surgery utilizing haptic feedback technology JOURNAL OF CLINICAL NEUROSCIENCE Thawani, J. P., Ramayya, A. G., Abdullah, K. G., Hudgins, E., Vaughan, K., Piazza, M., Madsen, P. J., Buch, V., Grady, M. 2016; 34: 112-116


    Simulated practice may improve resident performance in endoscopic endonasal surgery. Using the NeuroTouch haptic simulation platform, we evaluated resident performance and assessed the effect of simulation training on performance in the operating room. First- (N=3) and second- (N=3) year residents were assessed using six measures of proficiency. Using a visual analog scale, the senior author scored subjects. After the first session, subjects with lower scores were provided with simulation training. A second simulation served as a task-learning control. Residents were evaluated in the operating room over six months by the senior author-who was blinded to the trained/untrained identities-using the same parameters. A nonparametric bootstrap testing method was used for the analysis (Matlab v. 2014a). Simulation training was associated with an increase in performance scores in the operating room averaged over all measures (p=0.0045). This is the first study to evaluate the training utility of an endoscopic endonasal surgical task using a virtual reality haptic simulator. The data suggest that haptic simulation training in endoscopic neurosurgery may contribute to improvements in operative performance. Limitations include a small number of subjects and adjudication bias-although the trained/untrained identity of subjects was blinded. Further study using the proposed methods may better describe the relationship between simulated training and operative performance in endoscopic Neurosurgery.

    View details for DOI 10.1016/j.jocn.2016.05.036

    View details for Web of Science ID 000389093300023

    View details for PubMedID 27473019

  • Intramedullary Recurrence of a Thoracic Meningioma-Presentation of an Unusual Case and Review of the Literature. World neurosurgery Piazza, M. A., Ramayya, A. G., Geiger, G. A., Alonso-Basanta, M., Nasrallah, M. P., Welch, W. C., Ozturk, A. K. 2016; 92: 588.e17-588.e21


    Spinal meningiomas are typically extra-axial, slow-growing, benign tumors that arise from the arachnoid cap cells. Intramedullary spinal meningiomas are exceedingly rare with few cases reported in the literature.A 64-year-old man with a history of grade I thoracic meningioma at the T4 level resected initially in 1989 and who required reoperation in 2013 for intradural, extramedullary recurrence of tumor presented again in 2015 with gait difficulty. Magnetic resonance imaging revealed a soft tissue mass at the T3 to T4 levels on the left side of the canal that was mildly enhancing on T1 contrasted sequences. The patient was taken to the operating room, where a purely intramedullary recurrence was discovered without extramedullary extension or a dural-based attachment. The intramedullary tumor was completely resected, and postoperatively the patient recovered well and was at his neurologic baseline. The patient ultimately underwent proton beam radiotherapy because this tumor, although benign, had recurred twice.Intramedullary spinal meningiomas, particularly intramedullary low-grade recurrence of a previously extramedullary tumor, are rare phenomena. Although the pathogenic mechanisms are not well understood, intramedullary recurrence as described in this patient may reflect extrinsic factors related to prior surgical resections in addition to histologic progression. When operating on recurrent extramedullary lesions, aggressive arachnoid dissection may predispose patients to unusual patterns of recurrence.

    View details for DOI 10.1016/j.wneu.2016.01.073

    View details for PubMedID 26852709

  • Intraoperative Crisis Management in Spine Surgery: What To Do When Things Go Bad Benzel's Spine Surgery E-Book: Techniques, Complication Avoidance, and Management Ramayya, A., Abdullah, K., Tsai, E., Benzel, ., E.C. & Steinmetz, M. Elsevier Health Sciences. 2016
  • ). Adjacent Segment Degeneration and Disease of the Cervical and Lumbar Spine. Spine Surgery: Techniques, Complication Avoidance, and Management Benzel's Spine Surgery E-Book: Techniques, Complication Avoidance, and Management Ramayya, A., Abdullah, K., Mroz, T. Elsevier Health Sciences. 2016
  • Expectation modulates neural representations of valence throughout the human brain. NeuroImage Ramayya, A. G., Pedisich, I., Kahana, M. J. 2015; 115: 214-23


    The brain's sensitivity to unexpected gains or losses plays an important role in our ability to learn new behaviors (Rescorla and Wagner, 1972; Sutton and Barto, 1990). Recent work suggests that gains and losses are ubiquitously encoded throughout the human brain (Vickery et al., 2011), however, the extent to which reward expectation modulates these valence representations is not known. To address this question, we analyzed recordings from 4306 intracranially implanted electrodes in 39 neurosurgical patients as they performed a two-alternative probability learning task. Using high-frequency activity (HFA, 70-200 Hz) as an indicator of local firing rates, we found that expectation modulated reward-related neural activity in widespread brain regions, including regions that receive sparse inputs from midbrain dopaminergic neurons. The strength of unexpected gain signals predicted subjects' abilities to encode stimulus-reward associations. Thus, neural signals that are functionally related to learning are widely distributed throughout the human brain.

    View details for DOI 10.1016/j.neuroimage.2015.04.037

    View details for PubMedID 25937489

    View details for PubMedCentralID PMC4550220

  • Factors associated with increased survival after surgical resection of glioblastoma in octogenarians. PloS one Abdullah, K. G., Ramayya, A., Thawani, J. P., Macyszyn, L., Martinez-Lage, M., O'Rourke, D. M., Brem, S. 2015; 10 (5): e0127202


    Elderly patients with glioblastoma represent a clinical challenge for neurosurgeons and oncologists. The data available on outcomes of patients greater than 80 undergoing resection is limited. In this study, factors linked to increased survival in patients over the age of 80 were analyzed. A retrospective chart review of all patients over the age of 80 with a new diagnosis of glioblastoma and who underwent surgical resection with intent for maximal resection were examined. Patients who had only stereotactic biopsies were excluded. Immunohistochemical expression of oncogenic drivers (p53, EGFR, IDH-1) and a marker of cell proliferation (Ki-67 index) performed upon routine neuropathological examination were recorded. Stepwise logistic regression and Kaplan Meier survival curves were plotted to determine correlations to overall survival. Fifty-eight patients fit inclusion criteria with a mean age of 83 (range 80-93 years). The overall median survival was 4.2 months. There was a statistically significant correlation between Karnofsky Performance Status (KPS) and overall survival (P < 0.05). There was a significantly longer survival among patients undergoing either radiation alone or radiation and chemotherapy compared to those who underwent no postoperative adjuvant therapy (p < 0.05). There was also an association between overall survival and lack of p53 expression (p < 0.001) and lack of EGFR expression (p <0.05). In this very elderly population, overall survival advantage was conferred to those with higher preoperative KPS, postoperative adjuvant therapy, and lack of protein expression of EGFR and p53. These findings may be useful in clinical decision analysis for management of patients with glioblastoma who are octogenarians, and also validate the critical role of EGFR and p53 expression in oncogenesis, particularly with advancing age.

    View details for DOI 10.1371/journal.pone.0127202

    View details for PubMedID 25978638

    View details for PubMedCentralID PMC4433248

  • Human intracranial high-frequency activity during memory processing: neural oscillations or stochastic volatility? Current opinion in neurobiology Burke, J. F., Ramayya, A. G., Kahana, M. J. 2015; 31: 104-10


    Intracranial high-frequency activity (HFA), which refers to fast fluctuations in electrophysiological recordings, increases during memory processing. Two views have emerged to explain this effect: (1) HFA reflects a synchronous signal, related to underlying gamma oscillations, that plays a mechanistic role in human memory and (2) HFA reflects an asynchronous signal that is a non-specific marker of brain activation. We review recent data supporting each of these views and conclude that HFA during memory processing is more consistent with an asynchronous signal. Memory-related HFA is therefore best conceptualized as a biomarker of neural activation that can functionally map memory with high spatial and temporal precision.

    View details for DOI 10.1016/j.conb.2014.09.003

    View details for PubMedID 25279772

    View details for PubMedCentralID PMC4675136

  • Neurosurgery Schwartz's Principles of Surgery, 11th Edition Ramayya, A., Sinha, S., Grady, M. McGraw-Hill Medical. 2015
  • Electrophysiological evidence for functionally distinct neuronal populations in the human substantia nigra. Frontiers in human neuroscience Ramayya, A. G., Zaghloul, K. A., Weidemann, C. T., Baltuch, G. H., Kahana, M. J. 2014; 8: 655


    The human substantia nigra (SN) is thought to consist of two functionally distinct neuronal populations-dopaminergic (DA) neurons in the pars compacta subregion and GABA-ergic neurons in the pars reticulata subregion. However, a functional dissociation between these neuronal populations has not previously been demonstrated in the awake human. Here we obtained microelectrode recordings from the SN of patients undergoing deep brain stimulation (DBS) surgery for Parkinson's disease as they performed a two-alternative reinforcement learning task. Following positive feedback presentation, we found that putative DA and GABA neurons demonstrated distinct temporal dynamics. DA neurons demonstrated phasic increases in activity (250-500 ms post-feedback) whereas putative GABA neurons demonstrated more delayed and sustained increases in activity (500-1000 ms post-feedback). These results provide the first electrophysiological evidence for a functional dissociation between DA and GABA neurons in the human SN. We discuss possible functions for these neuronal responses based on previous findings in human and animal studies.

    View details for DOI 10.3389/fnhum.2014.00655

    View details for PubMedID 25249957

    View details for PubMedCentralID PMC4158808

  • Theta and high-frequency activity mark spontaneous recall of episodic memories. The Journal of neuroscience : the official journal of the Society for Neuroscience Burke, J. F., Sharan, A. D., Sperling, M. R., Ramayya, A. G., Evans, J. J., Healey, M. K., Beck, E. N., Davis, K. A., Lucas, T. H., Kahana, M. J. 2014; 34 (34): 11355-65


    Humans possess the remarkable ability to search their memory, allowing specific past episodes to be re-experienced spontaneously. Here, we administered a free recall test to 114 neurosurgical patients and used intracranial theta and high-frequency activity (HFA) to identify the spatiotemporal pattern of neural activity underlying spontaneous episodic retrieval. We found that retrieval evolved in three electrophysiological stages composed of: (1) early theta oscillations in the right temporal cortex, (2) increased HFA in the left hemisphere including the medial temporal lobe (MTL), left inferior frontal gyrus, as well as the ventrolateral temporal cortex, and (3) motor/language activation during vocalization of the retrieved item. Of these responses, increased HFA in the left MTL predicted recall performance. These results suggest that spontaneous recall of verbal episodic memories involves a spatiotemporal pattern of spectral changes across the brain; however, high-frequency activity in the left MTL represents a final common pathway of episodic retrieval.

    View details for DOI 10.1523/JNEUROSCI.2654-13.2014

    View details for PubMedID 25143616

    View details for PubMedCentralID PMC4138344

  • Microstimulation of the human substantia nigra alters reinforcement learning. The Journal of neuroscience : the official journal of the Society for Neuroscience Ramayya, A. G., Misra, A., Baltuch, G. H., Kahana, M. J. 2014; 34 (20): 6887-95


    Animal studies have shown that substantia nigra (SN) dopaminergic (DA) neurons strengthen action-reward associations during reinforcement learning, but their role in human learning is not known. Here, we applied microstimulation in the SN of 11 patients undergoing deep brain stimulation surgery for the treatment of Parkinson's disease as they performed a two-alternative probability learning task in which rewards were contingent on stimuli, rather than actions. Subjects demonstrated decreased learning from reward trials that were accompanied by phasic SN microstimulation compared with reward trials without stimulation. Subjects who showed large decreases in learning also showed an increased bias toward repeating actions after stimulation trials; therefore, stimulation may have decreased learning by strengthening action-reward associations rather than stimulus-reward associations. Our findings build on previous studies implicating SN DA neurons in preferentially strengthening action-reward associations during reinforcement learning.

    View details for DOI 10.1523/JNEUROSCI.5445-13.2014

    View details for PubMedID 24828643

    View details for PubMedCentralID PMC4019802

  • A DTI investigation of neural substrates supporting tool use. Cerebral cortex (New York, N.Y. : 1991) Ramayya, A. G., Glasser, M. F., Rilling, J. K. 2010; 20 (3): 507-16


    Recent functional neuroimaging and brain lesion studies have implicated a network of left hemisphere regions in human tool use: 1) posterior middle temporal cortex involved in conceptual knowledge of tools, 2) posterior inferior parietal cortex for representations of learned tool use gestures, and 3) anterior inferior parietal cortex, along with posterior inferior frontal and ventral premotor cortices, involved in grasping and manipulating objects. Here, we use diffusion tensor imaging (DTI) to investigate the anatomical connections that support this putative network. DTI scans were acquired from nineteen right-handed males and a deterministic tractography algorithm was used to identify connections between these regions implicated in tool use. Three of the resulting pathways were larger in the left than the right hemisphere. One connected posterior middle temporal cortex and the anterior inferior parietal cortex, a second connected posterior middle temporal cortex and the posterior inferior parietal cortex, and a third connected anterior inferior parietal cortex and the frontal lobe. In contrast, the connection between the posterior inferior parietal cortex and the frontal lobe was highly rightwardly asymmetric. Although further study is necessary to establish the functions of these pathways, we integrate our findings with previous evidence from functional neuroimaging and apraxia studies to suggest some possible functions.

    View details for DOI 10.1093/cercor/bhp141

    View details for PubMedID 19608779