Barriers to neurosurgery for medical students: a national study focused on the intersectionality of gender and race.

OBJECTIVE: Despite 51.2% of medical school graduates being female, only 29.8% of neurosurgery residency applicants are female. Furthermore, only 12.6% of neurosurgery applicants identify as underrepresented in medicine (URM). Evaluating the entry barriers for female and URM students is crucial in promoting the equity and diversity of the neurosurgical workforce. The objective of this study was to evaluate barriers to neurosurgery for medical students while considering the interaction between gender and race. METHODS: A Qualtrics survey was distributed widely to US medical students, assessing 14 factors of hesitancy toward neurosurgery. Likert scale responses, representing statement agreeability, converted to numeric values on a 7-point scale were analyzed by Mann-Whitney U-test and ANOVA comparisons with Bonferroni correction. RESULTS: Of 540 respondents, 68.7% were female and 22.6% were URM. There were 22.6% male non-URM, 7.4% male URM, 53.5% female non-URM, and 15.2% female URM respondents. The predominant reasons for hesitancy toward neurosurgery included work/life integration, length of training, competitiveness of residency position, and perceived malignancy of the field. Females were more hesitant toward neurosurgery due to maternity/paternity needs (p = 0.005), the absence of seeing people like them in the field (p < 0.001), and opportunities to pursue health equity work (p < 0.001). Females were more likely to have difficulties finding a mentor in neurosurgery who represented their identities (p = 0.017). URM students were more hesitant toward neurosurgery due to not seeing people like them in the field (p < 0.001). Subanalysis revealed that when students were stratified by both gender and URM status, there were more reasons for hesitancy toward neurosurgery that had significant differences between groups (male URM, male non-URM, female URM, and female non-URM students), suggesting the importance of intersectionality in this analysis. CONCLUSIONS: The authors highlight the implications of gender and racial diversity in the neurosurgical workforce on medical student interest and recruitment. Their findings suggest the importance of actively working to address these barriers, including 1) maternity/paternity policy reevaluation, standardization, and dissemination; and 2) actively providing resources for the creation of mentorship relationships for both women and URM students in an effort to create a workforce that aligns with the changing demographics of medical graduates to continue to improve diversity in neurosurgery.

Characterization of spatiotemporal dynamics of binary and graded tonic pain in humans using intracranial recordings.

Pain is a complex experience involving sensory, emotional, and cognitive aspects, and multiple networks manage its processing in the brain. Examining how pain transforms into a behavioral response can shed light on the networks' relationships and facilitate interventions to treat chronic pain. However, studies using high spatial and temporal resolution methods to investigate the neural encoding of pain and its psychophysical correlates have been limited. We recorded from intracranial stereo-EEG (sEEG) electrodes implanted in sixteen different brain regions of twenty patients who underwent psychophysical pain testing consisting of a tonic thermal stimulus to the hand. Broadband high-frequency local field potential amplitude (HFA; 70-150 Hz) was isolated to investigate the relationship between the ongoing neural activity and the resulting psychophysical pain evaluations. Two different generalized linear mixed-effects models (GLME) were employed to assess the neural representations underlying binary and graded pain psychophysics. The first model examined the relationship between HFA and whether the patient responded "yes" or "no" to whether the trial was painful. The second model investigated the relationship between HFA and how painful the stimulus was rated on a visual analog scale. GLMEs revealed that HFA in the inferior temporal gyrus (ITG), superior frontal gyrus (SFG), and superior temporal gyrus (STG) predicted painful responses at stimulus onset. An increase in HFA in the orbitofrontal cortex (OFC), SFG, and striatum predicted pain responses at stimulus offset. Numerous regions, including the anterior cingulate cortex, hippocampus, IFG, MTG, OFC, and striatum, predicted the pain rating at stimulus onset. However, only the amygdala and fusiform gyrus predicted increased pain ratings at stimulus offset. We characterized the spatiotemporal representations of binary and graded painful responses during tonic pain stimuli. Our study provides evidence from intracranial recordings that the neural encoding of psychophysical pain changes over time during a tonic thermal stimulus, with different brain regions being predictive of pain at the beginning and end of the stimulus.

Hemorrhagic Safety of Magnetic Resonance-Guided Focused Ultrasound Thalamotomy for Tremor without Interruption of Antiplatelet or Anticoagulant Therapy.

INTRODUCTION: Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy is an incision-less ablative technique used to treat medically refractory tremor. Although intracerebral hemorrhage has not been reported with MRgFUS thalamotomy for the treatment of movement disorders, clinicians commonly interrupt active blood thinning medications prior to the procedure or offer gamma knife radiosurgery instead. However, MRgFUS uses focal thermoablation, and bleeding risk is likely minimal. This study aimed to evaluate the safety of MRgFUS thalamotomy in patients with essential tremor (ET) and tremor-dominant Parkinson's disease (PD) without interrupting anticoagulant or antiplatelet therapies. METHODS: This was a single-center retrospective case series of all patients with ET or PD undergoing MRgFUS from February 2019 through December 2022 (n = 96). Demographic variables and medications taken at the time of surgery were obtained. Our primary outcome was the type and frequency of hemorrhagic complications noted on the operative report or postoperative imaging. RESULTS: The mean age of patients was 74.2 years, and 26% were female. Forty patients were taking ≥1 antiplatelet or anticoagulant medications. No patient actively taking anticoagulant or antiplatelet therapies had a hemorrhagic complication during or <48 h after the procedure. CONCLUSION: The frequency of intra- or postoperative complications from MRgFUS was not higher in patients actively taking anticoagulant or antiplatelet therapies relative to those who were not. Our findings suggest that MRgFUS thalamotomy does not necessitate interrupting anticoagulant or antiplatelet therapies. However, given the limited number of patients actively taking these therapies in our cohort (n = 40), additional testing in large, prospective studies should be conducted to further establish safety.

Initial case series of a novel sensing deep brain stimulation device in drug-resistant epilepsy and consistent identification of alpha/beta oscillatory activity: A feasibility study.

OBJECTIVE: Here, we report a retrospective, single-center experience with a novel deep brain stimulation (DBS) device capable of chronic local field potential (LFP) recording in drug-resistant epilepsy (DRE) and explore potential electrophysiological biomarkers that may aid DBS programming and outcome tracking. METHODS: Five patients with DRE underwent thalamic DBS, targeting either the bilateral anterior (n = 3) or centromedian (n = 2) nuclei. Postoperative electrode lead localizations were visualized in Lead-DBS software. Local field potentials recorded over 12-18 months were tracked, and changes in power were associated with patient events, medication changes, and stimulation. We utilized a combination of lead localization, in-clinic broadband LFP recordings, real-time LFP response to stimulation, and chronic recordings to guide DBS programming. RESULTS: Four patients (80%) experienced a >50% reduction in seizure frequency, whereas one patient had no significant reduction. Peaks in the alpha and/or beta frequency range were observed in the thalamic LFPs of each patient. Stimulation suppressed these LFP peaks in a dose-dependent manner. Chronic timeline data identified changes in LFP amplitude associated with stimulation, seizure occurrences, and medication changes. We also noticed a circadian pattern of LFP amplitudes in all patients. Button-presses during seizure events via a mobile application served as a digital seizure diary and were associated with elevations in LFP power. SIGNIFICANCE: We describe an initial cohort of patients with DRE utilizing a novel sensing DBS device to characterize potential LFP biomarkers of epilepsy that may be associated with seizure control after DBS in DRE. We also present a new workflow utilizing the Percept device that may optimize DBS programming using real-time and chronic LFP recording.

Characterization of spatiotemporal dynamics of binary and graded tonic pain in humans using intracranial recordings.

Pain is a complex experience involving sensory, emotional, and cognitive aspects, and multiple networks manage its processing in the brain. Examining how pain transforms into a behavioral response can shed light on the networks' relationships and facilitate interventions to treat chronic pain. However, studies using high spatial and temporal resolution methods to investigate the neural encoding of pain and its psychophysical correlates have been limited. We recorded from intracranial stereo-EEG (sEEG) electrodes implanted in sixteen different brain regions of twenty patients who underwent psychophysical pain testing consisting of a tonic thermal stimulus to the hand. Broadband high-frequency local field potential amplitude (HFA; 70-150 Hz) was isolated to investigate the relationship between the ongoing neural activity and the resulting psychophysical pain evaluations. Two different generalized linear mixed-effects models (GLME) were employed to assess the neural representations underlying binary and graded pain psychophysics. The first model examined the relationship between HFA and whether the patient responded "yes" or "no" to whether the trial was painful. The second model investigated the relationship between HFA and how painful the stimulus was rated on a visual analog scale. GLMEs revealed that HFA in the inferior temporal gyrus (ITG), superior frontal gyrus (SFG), and superior temporal gyrus (STG) predicted painful responses at stimulus onset. An increase in HFA in the orbitofrontal cortex (OFC), SFG, and striatum predicted pain responses at stimulus offset. Numerous regions including the anterior cingulate cortex, hippocampus, IFG, MTG, OFC, and striatum, predicted the pain rating at stimulus onset. However, only the amygdala and fusiform gyrus predicted increased pain ratings at stimulus offset. We characterized the spatiotemporal representations of binary and graded painful responses during tonic pain stimuli. Our study provides evidence from intracranial recordings that the neural encoding of psychophysical pain changes over time during a tonic thermal stimulus, with different brain regions being predictive of pain at the beginning and end of the stimulus.

Psychophysical pain encoding in the cingulate cortex predicts responsiveness of electrical stimulation.

Background: The anterior cingulate cortex (ACC) plays an important role in the cognitive and emotional processing of pain. Prior studies have used deep brain stimulation (DBS) to treat chronic pain, but results have been inconsistent. This may be due to network adaptation over time and variable causes of chronic pain. Identifying patient-specific pain network features may be necessary to determine patient candidacy for DBS. Hypothesis: Cingulate stimulation would increase patients' hot pain thresholds if non-stimulation 70-150 Hz activity encoded psychophysical pain responses. Methods: In this study, four patients who underwent intracranial monitoring for epilepsy monitoring participated in a pain task. They placed their hand on a device capable of eliciting thermal pain for five seconds and rated their pain. We used these results to determine the individual's thermal pain threshold with and without electrical stimulation. Two different types of generalized linear mixed-effects models (GLME) were employed to assess the neural representations underlying binary and graded pain psychophysics. Results: The pain threshold for each patient was determined from the psychometric probability density function. Two patients had a higher pain threshold with stimulation than without, while the other two patients had no difference. We also evaluated the relationship between neural activity and pain responses. We found that patients who responded to stimulation had specific time windows where high-frequency activity was associated with increased pain ratings. Conclusion: Stimulation of cingulate regions with increased pain-related neural activity was more effective at modulating pain perception than stimulating non-responsive areas. Personalized evaluation of neural activity biomarkers could help identify the best target for stimulation and predict its effectiveness in future studies evaluating DBS.

A novel thermoelectric device integrated with a psychophysical paradigm to study pain processing in human subjects.

INTRODUCTION: Cerebral projections of nociceptive stimuli are of great interest as targets for neuromodulation in chronic pain. To study cerebral networks involved in processing noxious stimuli, researchers often rely on thermo-nociception to induce pain. However, various limitations exist in many pain-inducing techniques, such as not accounting for individual variations in pain and trial structure predictability. METHODS: We propose an improved and reliable psychometric experimental method to evaluate human nociceptive processing to overcome some of these limitations. The developed testing paradigm leverages a custom-built, open-source, thermoelectric device (TED). The device construction and hardware are described. A maximum-likelihood adaptive algorithm is integrated into the TED software, facilitating individual psychometric functions representative of both hot and cold pain perception. In addition to testing only hot or cold thresholds, the TED may also be used to induce the thermal grill illusion (TGI), where the bars are set to alternating warm and cool temperatures. RESULTS: Here, we validated the TED's capability to adjust between different temperatures and showed that the device quickly and automatically changes temperature without any experimenter input. We also validated the device and integrated psychometric pain task in 21 healthy human subjects. Hot and cold pain thresholds (HPT, CPT) were determined in human subjects with <1 °C of variation. Thresholds were anticorrelated, meaning a volunteer with a low CPT likely had a high HPT. We also showed how the TED can be used to induce the TGI. CONCLUSION: The TED can induce thermo-nociception and provide probabilistic measures of hot and cold pain thresholds. Based on the findings presented, we discuss how the TED could be used to study thermo-nociceptive cerebral projections if paired with intracranial electrode monitoring.

Stochastic Resonance Governs Memory Consolidation Accuracy in a Neural Network Model.

The formation and recollection of memories is a multi-step neural process subject to errors. We propose a computational model of memory nodes receiving input from a colored tic-tac-toe board. We report memory errors during consolidation and reconsolidation when different noise levels are introduced into the model. The model is based on Hebbian plasticity and attempts to store the color and position of an X or O from the board. Memory nodes simulating neurons use an integrate-and-fire model to represent the correct or incorrect storage of the board information by scaling synaptic weights. We explored how baseline firing rate, which we considered analogous to noise in storing memory, impacted the creation of correct and incorrect memories. We found that a higher firing rate was associated with fewer accurate memories. Interestingly, the ideal amount of noise for correct memory storage was nonzero. This phenomenon is known as stochastic resonance, wherein random noise enhances processing. We also examined how many times our model could reactivate a memory before making an error. We found an exponentially decaying response, with a low firing rate yielding more stable memories. Even though our model incorporates only two memory nodes, it provides a basis for examining the consolidation and retrieval of memory storage based on the unique visual input of a tic-tac-toe board. Further work may incorporate different inputs, more nodes, and increased network complexity. Clinical Relevance- This model enables investigation of how the human cortex may utilize and exploit noise during information processing.

Corrigendum: LeGUI: A Fast and Accurate Graphical User Interface for Automated Detection and Anatomical Localization of Intracranial Electrodes.

[This corrects the article DOI: 10.3389/fnins.2021.769872.].

LeGUI: A Fast and Accurate Graphical User Interface for Automated Detection and Anatomical Localization of Intracranial Electrodes.

Accurate anatomical localization of intracranial electrodes is important for identifying the seizure foci in patients with epilepsy and for interpreting effects from cognitive studies employing intracranial electroencephalography. Localization is typically performed by coregistering postimplant computed tomography (CT) with preoperative magnetic resonance imaging (MRI). Electrodes are then detected in the CT, and the corresponding brain region is identified using the MRI. Many existing software packages for electrode localization chain together separate preexisting programs or rely on command line instructions to perform the various localization steps, making them difficult to install and operate for a typical user. Further, many packages provide solutions for some, but not all, of the steps needed for confident localization. We have developed software, Locate electrodes Graphical User Interface (LeGUI), that consists of a single interface to perform all steps needed to localize both surface and depth/penetrating intracranial electrodes, including coregistration of the CT to MRI, normalization of the MRI to the Montreal Neurological Institute template, automated electrode detection for multiple types of electrodes, electrode spacing correction and projection to the brain surface, electrode labeling, and anatomical targeting. The software is written in MATLAB, core image processing is performed using the Statistical Parametric Mapping toolbox, and standalone executable binaries are available for Windows, Mac, and Linux platforms. LeGUI was tested and validated on 51 datasets from two universities. The total user and computational time required to process a single dataset was approximately 1 h. Automatic electrode detection correctly identified 4362 of 4695 surface and depth electrodes with only 71 false positives. Anatomical targeting was verified by comparing electrode locations from LeGUI to locations that were assigned by an experienced neuroanatomist. LeGUI showed a 94% match with the 482 neuroanatomist-assigned locations. LeGUI combines all the features needed for fast and accurate anatomical localization of intracranial electrodes into a single interface, making it a valuable tool for intracranial electrophysiology research.

The Cerebral Localization of Pain: Anatomical and Functional Considerations for Targeted Electrical Therapies.

Millions of people in the United States are affected by chronic pain, and the financial cost of pain treatment is weighing on the healthcare system. In some cases, current pharmacological treatments may do more harm than good, as with the United States opioid crisis. Direct electrical stimulation of the brain is one potential non-pharmacological treatment with a long history of investigation. Yet brain stimulation has been far less successful than peripheral or spinal cord stimulation, perhaps because of our limited understanding of the neural circuits involved in pain perception. In this paper, we review the history of using electrical stimulation of the brain to treat pain, as well as contemporary studies identifying the structures involved in pain networks, such as the thalamus, insula, and anterior cingulate. We propose that the thermal grill illusion, an experimental pain model, can facilitate further investigation of these structures. Pairing this model with intracranial recording will provide insight toward disentangling the neural correlates from the described anatomic areas. Finally, the possibility of altering pain perception with brain stimulation in these regions could be highly informative for the development of novel brain stimulation therapies for chronic pain.

Development of the Implantable Resonator System for Clinical EPR Oximetry.

Hypoxic tumors are more resistant to radiotherapy and chemotherapy, which decreases the efficacy of these common forms of treatment. We have been developing implantable paramagnetic particulates to measure oxygen in vivo using electron paramagnetic resonance. Once implanted, oxygen can be measured repeatedly and non-invasively in superficial tissues (<3 cm deep), using an electron paramagnetic resonance spectrometer and an external surface-loop resonator. To significantly extend the clinical applications of electron paramagnetic resonance oximetry, we developed an implantable resonator system to obtain measurements at deeper sites. This system has been used to successfully obtain oxygen measurements in animal studies for several years. We report here on recent developments needed to meet the regulatory requirements to make this technology available for clinical use. radio frequency heating is discussed and magnetic resonance compatibility testing of the device has been carried out by a Good Laboratory Practice-certified laboratory. The geometry of the implantable resonator has been modified to meet our focused goal of verifying safety and efficacy for the proposed use of intracranial measurements and also for future use in tissue sites other than the brain. We have encapsulated the device within a smooth cylindrical-shaped silicone elastomer to prevent tissues from adhering to the device and to limit perturbation of tissue during implantation and removal. We have modified the configuration for simultaneously measuring oxygen at multiple sites by developing a linear array of oxygen sensing probes, which each provide independent measurements. If positive results are obtained in additional studies which evaluate biocompatibility and chemical characterization, we believe the implantable resonator will be at a suitable stage for initial testing in human subjects.

Assessment of ataxia phenotype in a new mouse model of galactose-1 phosphate uridylyltransferase (GALT) deficiency.

Despite adequate dietary management, patients with classic galactosemia continue to have increased risks of cognitive deficits, speech dyspraxia, primary ovarian insufficiency, and abnormal motor development. A recent evaluation of a new galactose-1 phosphate uridylyltransferase (GALT)-deficient mouse model revealed reduced fertility and growth restriction. These phenotypes resemble those seen in human patients. In this study, we further assess the fidelity of this new mouse model by examining the animals for the manifestation of a common neurological sequela in human patients: cerebellar ataxia. The balance, grip strength, and motor coordination of GALT-deficient and wild-type mice were tested using a modified rotarod. The results were compared to composite phenotype scoring tests, typically used to evaluate neurological and motor impairment. The data demonstrated abnormalities with varying severity in the GALT-deficient mice. Mice of different ages were used to reveal the progressive nature of motor impairment. The varying severity and age-dependent impairments seen in the animal model agree with reports on human patients. Finally, measurements of the cerebellar granular and molecular layers suggested that mutant mice experience cerebellar hypoplasia, which could have resulted from the down-regulation of the PI3K/Akt signaling pathway.