Binding of cortical functional modules by synchronous high-frequency oscillations.

Whether high-frequency phase-locked oscillations facilitate integration ('binding') of information across widespread cortical areas is controversial. Here we show with intracranial electroencephalography that cortico-cortical co-ripples (~100-ms-long ~90 Hz oscillations) increase during reading and semantic decisions, at the times and co-locations when and where binding should occur. Fusiform wordform areas co-ripple with virtually all language areas, maximally from 200 to 400 ms post-word-onset. Semantically specified target words evoke strong co-rippling between wordform, semantic, executive and response areas from 400 to 800 ms, with increased co-rippling between semantic, executive and response areas prior to correct responses. Co-ripples were phase-locked at zero lag over long distances (>12 cm), especially when many areas were co-rippling. General co-activation, indexed by non-oscillatory high gamma, was mainly confined to early latencies in fusiform and earlier visual areas, preceding co-ripples. These findings suggest that widespread synchronous co-ripples may assist the integration of multiple cortical areas for sustained periods during cognition.

Gamma amplitude-envelope correlations are strongly elevated within hyperexcitable networks in focal epilepsy.

Methods to quantify cortical hyperexcitability are of enormous interest for mapping epileptic networks in patients with focal epilepsy. We hypothesize that, in the resting state, cortical hyperexcitability increases firing-rate correlations between neuronal populations within seizure onset zones (SOZs). This hypothesis predicts that in the gamma frequency band (40-200 Hz), amplitude envelope correlations (AECs), a relatively straightforward measure of functional connectivity, should be elevated within SOZs compared to other areas. To test this prediction, we analyzed archived samples of interictal electrocorticographic (ECoG) signals recorded from patients who became seizure-free after surgery targeting SOZs identified by multiday intracranial recordings. We show that in the gamma band, AECs between nodes within SOZs are markedly elevated relative to those elsewhere. AEC-based node strength, eigencentrality, and clustering coefficient are also robustly increased within the SOZ with maxima in the low-gamma band (permutation test Z-scores > 8) and yield moderate discriminability of the SOZ using ROC analysis (maximal mean AUC ~ 0.73). By contrast to AECs, phase locking values (PLVs), a measure of narrow-band phase coupling across sites, and PLV-based graph metrics discriminate the seizure onset nodes weakly. Our results suggest that gamma band AECs may provide a clinically useful marker of cortical hyperexcitability in focal epilepsy.

Implementation of Exercise Management Services Among Sports Medicine Physicians in the United States.

OBJECTIVE: Assessment of physical activity and exercise prescription has been widely supported by many organizations, yet provision of such services remains limited in the United States. We sought to uncover why such services have not been widely adopted. DESIGN: The American Medical Society for Sports Medicine organized a task force to canvas physicians and survey the American Medical Society for Sports Medicine membership. SETTING: Peer-to-peer and telecommunication discussions and web-based questionnaires. PARTICIPANTS: Sports medicine physicians in the United States. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Percentage of sports medicine physicians who provide exercise management services and mechanisms of billing for exercise management, identify barriers to such services, and identify industry collaborations for promoting physical activity through physicians. RESULTS: Three of 4 sports medicine physicians spend at least 1 min encouraging exercise with patients, using Evaluation and Management codes to bill or receive credit. Exercise counseling is often bundled within other patient care. Few health plans leverage the patient's relationship with a primary care physician to promote exercise. Most employed sports medicine physicians do not receive incentives to incorporate exercise counseling into practice, and only 1 in 6 have decision-making authority to hire an exercise professional. Major obstacles are the lack of a business model and knowledge about exercise prescription. CONCLUSION: The existing E&M codes adequately characterize the work, but physicians desire greater payment or credit for providing exercise management services. Physicians desire to do more exercise prescription, but health system bureaucracy, inadequate support, and economic disincentives are barriers to the provision of exercise management services.

Binding of cortical functional modules by synchronous high frequency oscillations.

High-frequency phase-locked oscillations have been hypothesized to facilitate integration ('binding') of information encoded across widespread cortical areas. Ripples (~100ms long ~90Hz oscillations) co-occur ('co-ripple') broadly in multiple states and locations, but have only been associated with memory replay. We tested whether cortico-cortical co-ripples subserve a general role in binding by recording intracranial EEG during reading. Co-rippling increased to words versus consonant-strings between visual, wordform and semantic cortical areas when letters are binding into words, and words to meaning. Similarly, co-ripples strongly increased before correct responses between executive, response, wordform and semantic areas when word meanings bind instructions and response. Task-selective co-rippling dissociated from non-oscillatory activation and memory reinstatement. Co-ripples were phase-locked at zero-lag, even at long distances (>12cm), supporting a general role in cognitive binding.

No Geographic Distribution Change Among Residency Applicants in the Neurology Match During COVID-19.

Objectives The COVID-19 pandemic posed a novel challenge for the 2020-2021 Match cycle resulting in a virtual interview season. The advent of virtual interviews raised concerns for both programs and medical students. The possibility of an impact on the application strategies for medical students resulting in students being more likely to remain in the region or state of their medical school was considered. We investigated whether there was a change in the geographic distribution of residency applicants for the class of 2025 (matched in 2021) as compared to the previous three application cycles (classes of 2022-2024) across all 168 neurology residency programs within the United States. Methods Publicly available data from neurology program websites were compiled to record the location of resident medical schools and matched programs for the residency classes of 2022-2025. Missing or ambiguous information was cross-referenced to social media, (e.g. LinkedIn and Twitter). Statistical analyses were conducted utilizing SPSS 26 (IBM SPSS 26 Statistics for Windows, Armonk, NY).  Results Across all four classes, regional retention (students matching in the same region) was 70.2% for the Northeast, 59.6% for the Midwest, 52.9% for the South, and 59.4% for the West. No significant change between the residency class of 2025 and the previous three classes was present. Discussion No significant change to the geographic trends for candidates was seen with the virtual interview process for the 2020-2021 neurology Match. As has been seen in other fields, a strong regional preference, with the majority of residents matching to programs in the same regions as their medical school, was seen for neurology.

Responsive Neurostimulation of the Anterior Thalamic Nuclei in Refractory Genetic Generalized Epilepsy: A Case Series.

Genetic generalized epilepsies (GGEs) are thought to represent disorders of thalamocortical networks. There are currently no well-established non-pharmacologic treatment options for patients with drug-resistant GGE. NeuroPace's Responsive Neurostimulation (RNS) System was approved by the United States Food and Drug Administration to treat focal seizures with up to two ictal foci. We report on three adults with drug-resistant GGE who were treated with thalamic RNS. Given the severity of their epilepsies and the potential ictogenic role of the thalamus in the pathophysiology of GGE, the RNS System was palliatively implanted with leads in the bilateral anterior thalamic nuclei (ANT) of these patients. The ANT was selected because it was demonstrated to be a safe target. We retrospectively evaluated metrics including seizure frequency over 18-32 months. One patient required explantation due to infection. The other two patients were clinical responders. By the end of the observation period reported here, one patient was seizure-free for over 9 months. All three self-reported an improved quality of life. The clinical response observed in these patients provides 'proof-of-principle' that GGE may be treatable with responsive thalamic stimulation. Our results support proceeding to a larger study investigating the efficacy and safety of thalamic RNS in drug-resistant GGE.

Late dominance of the right hemisphere during narrative comprehension.

PET and fMRI studies suggest that auditory narrative comprehension is supported by a bilateral multilobar cortical network. The superior temporal resolution of magnetoencephalography (MEG) makes it an attractive tool to investigate the dynamics of how different neuroanatomic substrates engage during narrative comprehension. Using beta-band power changes as a marker of cortical engagement, we studied MEG responses during an auditory story comprehension task in 31 healthy adults. The protocol consisted of two runs, each interleaving 7 blocks of the story comprehension task with 15 blocks of an auditorily presented math task as a control for phonological processing, working memory, and attention processes. Sources at the cortical surface were estimated with a frequency-resolved beamformer. Beta-band power was estimated in the frequency range of 16-24 Hz over 1-sec epochs starting from 400 msec after stimulus onset until the end of a story or math problem presentation. These power estimates were compared to 1-second epochs of data before the stimulus block onset. The task-related cortical engagement was inferred from beta-band power decrements. Group-level source activations were statistically compared using non-parametric permutation testing. A story-math contrast of beta-band power changes showed greater bilateral cortical engagement within the fusiform gyrus, inferior and middle temporal gyri, parahippocampal gyrus, and left inferior frontal gyrus (IFG) during story comprehension. A math-story contrast of beta power decrements showed greater bilateral but left-lateralized engagement of the middle frontal gyrus and superior parietal lobule. The evolution of cortical engagement during five temporal windows across the presentation of stories showed significant involvement during the first interval of the narrative of bilateral opercular and insular regions as well as the ventral and lateral temporal cortex, extending more posteriorly on the left and medially on the right. Over time, there continued to be sustained right anterior ventral temporal engagement, with increasing involvement of the right anterior parahippocampal gyrus, STG, MTG, posterior superior temporal sulcus, inferior parietal lobule, frontal operculum, and insula, while left hemisphere engagement decreased. Our findings are consistent with prior imaging studies of narrative comprehension, but in addition, they demonstrate increasing right-lateralized engagement over the course of narratives, suggesting an important role for these right-hemispheric regions in semantic integration as well as social and pragmatic inference processing.

Anti-seizure medication treatment trials prior to pre-surgical evaluation.

Purpose: Our study evaluates patterns of anti-seizure medication (ASM) usage prior to pre-surgical evaluation in drug resistant epilepsy (DRE). Methods: We conducted a retrospective study of patients with DRE presenting for pre-surgical evaluation from 1/1/2017 to 12/31/2018. We abstracted demographic data, ASM usage, MRI and EEG findings, and distance from home to our center. Results: In total, 54 patients (23 female) were included. The mean number of ASM trials at the time of pre-surgical evaluation was 5.62 (±3.3; range 1-15). A mean of 0.4 ASMs (±1.1; range 0-6) were initiated at our center prior to pre-surgical evaluation. MRI localization to regions other than the hippocampal or temporal region (p = 0.002) was associated with higher numbers of ASM trials. A trend for a larger number of ASM trials was seen for increased distance of patient primary residence from our center, right-sided ictal EEG laterality, and posterior quadrant or non-localized ictal EEG patterns. Conclusions: Only 17% of patients were referred for pre-surgical evaluation after a trial of 1-2 ASMs. On average, patients tried 5.6 different ASMs with most of those trials predating referral to our center. Temporal lobe lesions were associated with fewer ASM trials prior to referral. Female sex was associated with an average of two more ASM trials than males. Our data do not allow us to determine how access to care, patient choice, and physician opinions impact the variability of ASM trials prior to referral for surgical evaluation. Our data indicate that delays to pre-surgical evaluation continue to occur.

Epilepsy Milestones 2.0: An updated framework for assessing epilepsy fellowships and fellows.

OBJECTIVE: Accreditation Council for Graduate Medical Education (ACGME)-accredited epilepsy fellowships, like other ACGME accredited training programs, use Milestones to establish learning objectives and to evaluate how well trainees are achieving these goals. The ACGME began developing the second iteration of the Milestones 6 years ago, and these are now being adapted to all specialties. Here, we describe the process by which Epilepsy Milestones 2.0 were developed and summarize them. METHODS: A work group of nine board-certified, adult and pediatric epileptologists reviewed Epilepsy Milestones 1.0 and revised them using a modified Delphi approach. RESULTS: The new Milestones share structural changes with all other specialties, including a clearer stepwise progression in professional development and the harmonized Milestones that address competencies common to all medical fields. Much of the epilepsy-specific content remains the same, although a major addition is a set of Milestones focused on reading and interpreting electroencephalograms (EEGs), which the old Milestones lacked. Epilepsy Milestones 2.0 includes a Supplemental Guide to help program directors implement the new Milestones. Together, Epilepsy Milestones 2.0 and the Supplemental Guide recognize advances in epilepsy, including stereo-EEG, neurostimulation, genetics, and safety in epilepsy monitoring units. SIGNIFICANCE: Epilepsy Milestones 2.0 address the shortcomings of the old Milestones and should facilitate the assessment of epilepsy fellowships and fellows by program directors, faculty, and fellows themselves.

Prediction of Naming Outcome With fMRI Language Lateralization in Left Temporal Epilepsy Surgery.

BACKGROUND AND OBJECTIVES: Naming decline after left temporal lobe epilepsy (TLE) surgery is common and difficult to predict. Preoperative language fMRI may predict naming decline, but this application is still lacking evidence. We performed a large multicenter cohort study of the effectiveness of fMRI in predicting naming deficits after left TLE surgery. METHODS: At 10 US epilepsy centers, 81 patients with left TLE were prospectively recruited and given the Boston Naming Test (BNT) before and ≈7 months after anterior temporal lobectomy. An fMRI language laterality index (LI) was measured with an auditory semantic decision-tone decision task contrast. Correlations and a multiple regression model were built with a priori chosen predictors. RESULTS: Naming decline occurred in 56% of patients and correlated with fMRI LI (r = -0.41, p < 0.001), age at epilepsy onset (r = -0.30, p = 0.006), age at surgery (r = -0.23, p = 0.039), and years of education (r = 0.24, p = 0.032). Preoperative BNT score and duration of epilepsy were not correlated with naming decline. The regression model explained 31% of the variance, with fMRI contributing 14%, with a 96% sensitivity and 44% specificity for predicting meaningful naming decline. Cross-validation resulted in an average prediction error of 6 points. DISCUSSION: An fMRI-based regression model predicted naming outcome after left TLE surgery in a large, prospective multicenter sample, with fMRI as the strongest predictor. These results provide evidence supporting the use of preoperative language fMRI to predict language outcome in patients undergoing left TLE surgery. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that fMRI language lateralization can help in predicting naming decline after left TLE surgery.

The Precentral Gyrus Contributions to the Early Time-Course of Grapheme-to-Phoneme Conversion.

As part of silent reading models, visual orthographic information is transduced into an auditory phonological code in a process of grapheme-to-phoneme conversion (GPC). This process is often identified with lateral temporal-parietal regions associated with auditory phoneme encoding. However, the role of articulatory phonemic representations and the precentral gyrus in GPC is ambiguous. Though the precentral gyrus is implicated in many functional MRI studies of reading, it is not clear if the time course of activity in this region is consistent with the precentral gyrus being involved in GPC. We recorded cortical electrophysiology during a bimodal match/mismatch task from eight patients with perisylvian subdural electrodes to examine the time course of neural activity during a task that necessitated GPC. Patients made a match/mismatch decision between a 3-letter string and the following auditory bi-phoneme. We characterized the distribution and timing of evoked broadband high gamma (70-170 Hz) as well as phase-locking between electrodes. The precentral gyrus emerged with a high concentration of broadband high gamma responses to visual and auditory language as well as mismatch effects. The pars opercularis, supramarginal gyrus, and superior temporal gyrus were also involved. The precentral gyrus showed strong phase-locking with the caudal fusiform gyrus during letter-string presentation and with surrounding perisylvian cortex during the bimodal visual-auditory comparison period. These findings hint at a role for precentral cortex in transducing visual into auditory codes during silent reading.

A systems-level analysis highlights microglial activation as a modifying factor in common epilepsies.

AIMS: The causes of distinct patterns of reduced cortical thickness in the common human epilepsies, detectable on neuroimaging and with important clinical consequences, are unknown. We investigated the underlying mechanisms of cortical thinning using a systems-level analysis. METHODS: Imaging-based cortical structural maps from a large-scale epilepsy neuroimaging study were overlaid with highly spatially resolved human brain gene expression data from the Allen Human Brain Atlas. Cell-type deconvolution, differential expression analysis and cell-type enrichment analyses were used to identify differences in cell-type distribution. These differences were followed up in post-mortem brain tissue from humans with epilepsy using Iba1 immunolabelling. Furthermore, to investigate a causal effect in cortical thinning, cell-type-specific depletion was used in a murine model of acquired epilepsy. RESULTS: We identified elevated fractions of microglia and endothelial cells in regions of reduced cortical thickness. Differentially expressed genes showed enrichment for microglial markers and, in particular, activated microglial states. Analysis of post-mortem brain tissue from humans with epilepsy confirmed excess activated microglia. In the murine model, transient depletion of activated microglia during the early phase of the disease development prevented cortical thinning and neuronal cell loss in the temporal cortex. Although the development of chronic seizures was unaffected, the epileptic mice with early depletion of activated microglia did not develop deficits in a non-spatial memory test seen in epileptic mice not depleted of microglia. CONCLUSIONS: These convergent data strongly implicate activated microglia in cortical thinning, representing a new dimension for concern and disease modification in the epilepsies, potentially distinct from seizure control.

An Intracranial Electrophysiology Study of Visual Language Encoding: The Contribution of the Precentral Gyrus to Silent Reading.

Models of reading emphasize that visual (orthographic) processing provides input to phonological as well as lexical-semantic processing. Neurobiological models of reading have mapped these processes to distributed regions across occipital-temporal, temporal-parietal, and frontal cortices. However, the role of the precentral gyrus in these models is ambiguous. Articulatory phonemic representations in the precentral gyrus are obviously involved in reading aloud, but it is unclear if the precentral gyrus is recruited during reading silently in a time window consistent with participation in phonological processing contributions. Here, we recorded intracranial electrophysiology during a speeded semantic decision task from 24 patients to map the spatio-temporal flow of information across the cortex during silent reading. Patients selected animate nouns from a stream of nonanimate words, letter strings, and false-font stimuli. We characterized the distribution and timing of evoked high-gamma power (70-170 Hz) as well as phase-locking between electrodes. The precentral gyrus showed a proportion of electrodes responsive to linguistic stimuli (27%) that was at least as high as those of surrounding peri-sylvian regions. These precentral gyrus electrodes had significantly greater high-gamma power for words compared to both false-font and letter-string stimuli. In a patient with word-selective effects in the fusiform, superior temporal, and precentral gyri, there was significant phase-locking between the fusiform and precentral gyri starting at ∼180 msec and between the precentral and superior temporal gyri starting at ∼220 msec. Finally, our large patient cohort allowed exploratory analyses of the spatio-temporal reading network underlying silent reading. The distribution, timing, and connectivity results place the precentral gyrus as an important hub in the silent reading network.

Future of Neurology & Technology: Virtual and Augmented Reality in Neurology and Neuroscience Education: Applications and Curricular Strategies.

Virtual reality and augmented reality have become increasingly prevalent in our lives. They are changing the way we see and interact with the world and have started percolating medical education. In this article, we reviewed key applications of virtual and augmented realities in neurology and neuroscience education, and discussed barriers and opportunities for implementation in the curriculum. Although long-term benefits of these approaches over more traditional learning methods and the optimal curricular balance remain mostly unexplored, virtual and augmented reality can change how we teach neurology and neuroscience.

You never forget your first? Impact of interview timing on institutional rank order.

OBJECTIVE: To analyze the impact of interview date on the applicant rank for Neurology residencies in the United States. METHODS: A multi-institutional retrospective review of interview dates and applicant rank list data for the National Resident Matching Program (NRMP) was conducted for five Neurology programs, totaling 1932 interviewed applicants over a combined total of 31 interview years. For each candidate, the interview date and applicant rank were abstracted along with the total number of interviews for that season. Statistical analyses were completed on the cumulative institution data set as well for each individual institution to assess for a possible relationship between interview date and applicant rank. RESULTS: The cumulative institutional analysis showed that the mean applicant rank decreased as the interview season progressed. Applicants who interviewed on the first day of the interview season were ranked 11.4% higher than those who interviewed on the last interview day. Additionally, applicants interviewed on the first interview day more likely to be ranked higher when compared to all other interview dates. Independent analysis of each program's data identified comparable, statistically significant, differences in mean applicant rank and interview position at three out of the five institutions. CONCLUSIONS: This study evaluated the impact of interview order on the ranking of applicants by Neurology residency programs, noting a temporal relationship with applicant rank and interview date. The primacy bias appreciated in our data merits further evaluation in other medical specialties. Strategies to minimize the impact of this bias should be employed by residency programs who use medical matching services.

Sexual violence in sport: American Medical Society for Sports Medicine Position Statement.

The American Medical Society for Sports Medicine (AMSSM) convened a group of experts to develop a Position Statement addressing the problem of sexual violence in sport. The AMSSM Sexual Violence in Sport Task Force held a series of meetings over 7 months, beginning in July 2019. Following a literature review, the Task Force used an iterative process and expert consensus to finalise the Position Statement. The objective of this Position Statement is to raise awareness of this critical issue among sports medicine physicians and to declare a commitment to engage in collaborative, multidisciplinary solutions to reduce sexual violence in sport.

Temporal lobe regions essential for preserved picture naming after left temporal epilepsy surgery.

OBJECTIVE: To define left temporal lobe regions where surgical resection produces a persistent postoperative decline in naming visual objects. METHODS: Pre- and postoperative brain magnetic resonance imaging data and picture naming (Boston Naming Test) scores were obtained prospectively from 59 people with drug-resistant left temporal lobe epilepsy. All patients had left hemisphere language dominance at baseline and underwent surgical resection or ablation in the left temporal lobe. Postoperative naming assessment occurred approximately 7 months after surgery. Surgical lesions were mapped to a standard template, and the relationship between presence or absence of a lesion and the degree of naming decline was tested at each template voxel while controlling for effects of overall lesion size. RESULTS: Patients declined by an average of 15% in their naming score, with wide variation across individuals. Decline was significantly related to damage in a cluster of voxels in the ventral temporal lobe, located mainly in the fusiform gyrus approximately 4-6 cm posterior to the temporal tip. Extent of damage to this region explained roughly 50% of the variance in outcome. Picture naming decline was not related to hippocampal or temporal pole damage. SIGNIFICANCE: The results provide the first statistical map relating lesion location in left temporal lobe epilepsy surgery to picture naming decline, and they support previous observations of transient naming deficits from electrical stimulation in the basal temporal cortex. The critical lesion is relatively posterior and could be avoided in many patients undergoing left temporal lobe surgery for intractable epilepsy.

Sexual Violence in Sport: American Medical Society for Sports Medicine Position Statement.

The American Medical Society for Sports Medicine (AMSSM) convened a group of experts to develop a position statement addressing the problem of sexual violence in sport. The AMSSM Sexual Violence in Sport Task Force held a series of meetings over 7 months, beginning in July 2019. Following a literature review, the task force used an iterative process and expert consensus to finalize the position statement. The objective of this position statement is to raise awareness of this critical issue among sports medicine physicians and to declare a commitment to engage in collaborative, multidisciplinary solutions to reduce sexual violence in sport.

Anti-myelin oligodendrocyte glycoprotein (MOG) associated disease masquerading as prolonged intractable nausea and vomiting.

The clinical and radiological spectrum of myelin oligodendrocyte glycoprotein (MOG) antibody associated disease continues to expand. Here, we describe a case of prolonged, relapsing, intractable nausea and vomiting misdiagnosed as a functional disorder for more than one year. The patient did not receive a neurological workup until clear neurological signs developed. This case exemplifies the delay in diagnosis when neurological disease presents with seemingly non-neurological symptoms and illustrates brainstem and upper spinal cord radiological findings that can help guide the treating physician to test for MOG antibodies and provide the appropriate treatment.

Sexual Violence in Sport: American Medical Society for Sports Medicine Position Statement.

The American Medical Society for Sports Medicine (AMSSM) convened a group of experts to develop a Position Statement addressing the problem of sexual violence in sport. The AMSSM Sexual Violence in Sport Task Force held a series of meetings over 7 months, beginning in July 2019. Following a literature review, the task force used an iterative process and expert consensus to finalize the position statement. The objective of this position statement is to raise awareness of this critical issue among sports medicine physicians and to declare a commitment to engage in collaborative, multidisciplinary solutions to reduce sexual violence in sport.