Biomechanical Predictors of Sacroiliac Joint Uptake on SPECT/CT.

OBJECTIVE: Single Photon Emission Computed Tomography/ Computed Tomography (SPECT/CT) is an emerging imaging modality that identifies sites of heightened bone metabolism in response to increased stresses. The relationship between sacroiliac joint (SI) radiotracer uptake and anatomic biomechanical parameters is poorly understood. METHODS: Adult patients with SPECT/CT scans performed at our institution between 2021-2023 for the workup of low back pain were included. Patient charts were reviewed for demographic factors, including age, gender, and prior thoracolumbar fusion history. Biomechanical spinopelvic parameters were measured from standing scoliosis x-rays. SPECT/CT scans were reviewed for uptake at the SI joint. Patients were stratified into two cohorts; patients with SI uptake greater than iliac crest uptake were designated "hot," whereas those with less or equal uptake were labeled "cold." RESULTS: 160 patients met inclusion criteria. Patients were slightly more male (55%) with average age 55 ± 14.9 years. 68 patients (43%) had evidence of increased SI activity. Interrater reliability showed substantial agreement (kappa = 0.62). The hot cohort demonstrated greater pelvic incidence (54.8 ± 14.0° vs. 51.0 ± 11.0°, p = 0.031) and pelvic tilt (20.8 ± 9.5° vs. 18.4 ± 8.6°, p =0.047) compared to the cold cohort. Patients were otherwise similar between cohorts (p >0.05). CONCLUSIONS: Increased pelvic incidence and pelvic tilt angles are associated with SPECT/CT uptake at the SIJ, which may reflect altered biomechanics at the spinopelvic junction. SPECT/CT may be a valuable tool to assess SI degeneration. Future studies are warranted to better characterize the clinical applications of these findings.

Clear neuroimaging margin at the brain-tumor interface is associated with gross total resection and longer survival in non-enhancing diffuse gliomas.

BACKGROUND: This study aimed to determine whether the presence of distinct glioma margins on preoperative imaging is correlated with improved intraoperative identification of tumor-brain interfaces and overall improved surgical outcomes of non-enhancing gliomas. METHODS: This is a retrospective study of all primary glioma resections at our institution between 2000-2020. Tumors with contrast enhancement or with final pathology other than diffuse infiltrative glial neoplasm (WHO II or WHO III) were excluded. Tumors were stratified into two groups: those with distinct radiographical borders between tumor and brain, and those with ill-defined radiographical margins. Multivariate analysis was performed to determine the impact of clear preoperative margins on the primary outcome of gross-total resection. RESULTS: Within the study period, 59 patients met inclusion criteria, of which 31 (53%) had distinct margins. These patients were predominantly younger (37.6 vs. 48.1 years, P=0.007). Tumor and other patient characteristics were similar in both cohorts, including gender, laterality, size, location, tumor type, grade, and surgical adjuncts utilized (P>0.05). Multivariate regression identified that distinct preoperative margins correlated with increased rates of gross total resection (P=0.02). Distinct margins on preoperative neuroimaging also correlated positively with surgeon identification of intra-operative margins (P<0.0001), fewer deaths over the study period (P=0.01), and longer overall survival (P=0.03). CONCLUSIONS: Distinct glioma-parenchyma margins on preoperative imaging are associated with improved surgical resection for diffuse gliomas, as distinct margins may correlate with distinguishable glioma-brain interfaces intraoperatively. Further prospective studies may discover additional clinical uses for these findings.

Association of geographical disparities and segregation in regional treatment facilities for Black patients with aneurysmal subarachnoid hemorrhage in the United States.

Background and objectives: This study investigates geographic disparities in aneurysmal subarachnoid hemorrhage (aSAH) care for Black patients and aims to explore the association with segregation in treatment facilities. Understanding these dynamics can guide efforts to improve healthcare outcomes for marginalized populations. Methods: This cohort study evaluated regional differences in segregation for Black patients with aSAH and the association with geographic variations in disparities from 2016 to 2020. The National Inpatient Sample (NIS) database was queried for admission data on aSAH. Black patients were compared to White patients. Segregation in treatment facilities was calculated using the dissimilarity (D) index. Using multivariable logistic regression models, the regional disparities in aSAH treatment, functional outcomes, mortality, and end-of-life care between Black and White patients and the association of geographical segregation in treatment facilities was assessed. Results: 142,285 Black and White patients were diagnosed with aSAH from 2016 to 2020. The Pacific division (D index = 0.55) had the greatest degree of segregation in treatment facilities, while the South Atlantic (D index = 0.39) had the lowest. Compared to lower segregation, regions with higher levels of segregation (global F test p < 0.001) were associated a lower likelihood of mortality (OR 0.91, 95% CI 0.82-1.00, p = 0.044 vs. OR 0.75, 95% CI 0.68-0.83, p < 0. 001) (p = 0.049), greater likelihood of tracheostomy tube placement (OR 1.45, 95% CI 1.22-1.73, p < 0.001 vs. OR 1.87, 95% CI 1.59-2.21, p < 0.001) (p < 0. 001), and lower likelihood of receiving palliative care (OR 0.88, 95% CI 0.76-0.93, p < 0.001 vs. OR 0.67, 95% CI 0.59-0.77, p < 0.001) (p = 0.029). Conclusion: This study demonstrates regional differences in disparities for Black patients with aSAH, particularly in end-of-life care, with varying levels of segregation in regional treatment facilities playing an associated role. The findings underscore the need for targeted interventions and policy changes to address systemic healthcare inequities, reduce segregation, and ensure equitable access to high-quality care for all patients.

Identifying Distinct Neural Features between the Initial and Corrective Phases of Precise Reaching Using AutoLFADS.

Many initial movements require subsequent corrective movements, but how the motor cortex transitions to make corrections and how similar the encoding is to initial movements is unclear. In our study, we explored how the brain's motor cortex signals both initial and corrective movements during a precision reaching task. We recorded a large population of neurons from two male rhesus macaques across multiple sessions to examine the neural firing rates during not only initial movements but also subsequent corrective movements. AutoLFADS, an autoencoder-based deep-learning model, was applied to provide a clearer picture of neurons' activity on individual corrective movements across sessions. Decoding of reach velocity generalized poorly from initial to corrective submovements. Unlike initial movements, it was challenging to predict the velocity of corrective movements using traditional linear methods in a single, global neural space. We identified several locations in the neural space where corrective submovements originated after the initial reaches, signifying firing rates different than the baseline before initial movements. To improve corrective movement decoding, we demonstrate that a state-dependent decoder incorporating the population firing rates at the initiation of correction improved performance, highlighting the diverse neural features of corrective movements. In summary, we show neural differences between initial and corrective submovements and how the neural activity encodes specific combinations of velocity and position. These findings are inconsistent with assumptions that neural correlations with kinematic features are global and independent, emphasizing that traditional methods often fall short in describing these diverse neural processes for online corrective movements.

Identifying distinct neural features between the initial and corrective phases of precise reaching using AutoLFADS.

Many initial movements require subsequent corrective movements, but how motor cortex transitions to make corrections and how similar the encoding is to initial movements is unclear. In our study, we explored how the brain's motor cortex signals both initial and corrective movements during a precision reaching task. We recorded a large population of neurons from two male rhesus macaques across multiple sessions to examine the neural firing rates during not only initial movements but also subsequent corrective movements. AutoLFADS, an auto-encoder-based deep-learning model, was applied to provide a clearer picture of neurons' activity on individual corrective movements across sessions. Decoding of reach velocity generalized poorly from initial to corrective submovements. Unlike initial movements, it was challenging to predict the velocity of corrective movements using traditional linear methods in a single, global neural space. We identified several locations in the neural space where corrective submovements originated after the initial reaches, signifying firing rates different than the baseline before initial movements. To improve corrective movement decoding, we demonstrate that a state-dependent decoder incorporating the population firing rates at the initiation of correction improved performance, highlighting the diverse neural features of corrective movements. In summary, we show neural differences between initial and corrective submovements and how the neural activity encodes specific combinations of velocity and position. These findings are inconsistent with assumptions that neural correlations with kinematic features are global and independent, emphasizing that traditional methods often fall short in describing these diverse neural processes for online corrective movements. Significance Statement: We analyzed submovement neural population dynamics during precision reaching. Using an auto- encoder-based deep-learning model, AutoLFADS, we examined neural activity on a single-trial basis. Our study shows distinct neural dynamics between initial and corrective submovements. We demonstrate the existence of unique neural features within each submovement class that encode complex combinations of position and reach direction. Our study also highlights the benefit of state-specific decoding strategies, which consider the neural firing rates at the onset of any given submovement, when decoding complex motor tasks such as corrective submovements.

Endovascular thrombectomy for posterior cerebral artery strokes in the national inpatient sample (EaT PeCANpIeS) study.

BACKGROUND: Posterior cerebral arteries with acute ischemic strokes (PCA-AISs) comprise around 2% of all acute ischemic strokes and may result in significant long-term deficits. Current guidance regarding endovascular thrombectomy (EVT) for PCA-AIS is insufficient as no published randomized trials exist. METHODS: An analysis of the National Inpatient Sample database compared medical management versus EVT for PCA-AIS. Propensity score matching was applied to adjust for nonrandomization. RESULTS: The study included 19,655 patients. Before matching, the EVT cohort had significantly higher National Institutes of Health Stroke Scale (NIHSS) (10.21 vs. 4.67, p < 0.001), had lower rates of favorable functional outcomes, functional independence, and higher rates of intracranial hemorrhage (ICH) and inpatient mortality. After matching, no differences in functional outcomes were identified, but revealed a higher proportion of ICH in the EVT group (17.45% vs. 8.98%, p < 0.001). However, NIHSS subgroup analysis identified improved functional outcomes associated with the EVT group who presented with an NIHSS between 10 and 19 both in terms of rates of favorable functional outcomes (35.56% vs. 12.09%, p < 0.001) and rates of functional independence (26.67% vs. 9.34%, p < 0.01). On further investigation, the clinical benefit, in the NIHSS 10-19 subgroup, was driven by patients receiving EVT in combination with intravenous thrombolysis (IVT). CONCLUSIONS: This analysis shows that current national practices utilize EVT for more severe PCA strokes. Clinical benefit was only detected in patients with moderate stroke severity (NIHSS 10-19) who were treated with combined EVT and IVT. Further work is needed to investigate the features of PCA-AIS that might benefit from EVT the most.

Virtual Interviews During COVID-19 Changed Neurosurgery Match-for Better or Worse.

OBJECTIVE: The COVID-19 pandemic forced neurosurgery residency application processes to adopt a virtual interview model. This study analyzes the trends in program and applicant residency match behavior due to virtual interviews. METHODS: National Resident Matching Program data from Main Residency Match, National Resident Matching Program Director and Applicant Survey, Electronic Residency Application Service, and Charting Outcomes in the Match were collected for neurosurgery residents for all available years, providing information on neurosurgery residency application, interview, and match outcomes. Studied years were dichotomized to account for virtual versus in-person interviews and analyzed for differences. RESULTS: Although the average number of applications received during in-person versus virtual years was not statistically different, 245 versus 290 (P = 0.115), programs interviewed more applicants when interviews were virtual, 37.2 versus 46, (P = 0.008). Similarly, matched U.S. senior applicants did not submit a statistically higher number of applications in person versus virtual, 54 versus 77 (P = 0.055), but they did attend more interviews virtually, 20.5 versus 16.6 (P = 0.013), and ranked more programs, 20 versus 16.2 (P = 0.002). Although White applicants did not have a statistically significant difference in number of applications submitted (55 vs. 68, P = 0.129), Black applicants submitted more applications during virtual match compared with in-person match (52 vs. 74, P = 0.012). The number of applicants that programs needed to rank to fill each position was not statistically different when comparing in-person versus virtually conducted interviews, 4.6 versus 5.4 (P = 0.070). CONCLUSIONS: Despite no change in the overall number of applications submitted per applicant, Black applicants submitted more applications virtually, suggesting potential benefits of virtual format for Black applicants. Interview format was strongly correlated to the use of perceived fitness by applicants in rank decision making. Virtual interviews provide major financial advantages to candidates and could help improve Black representation in neurosurgery. However, they impose limitations on ability access fitness.

Repeated passive visual experience modulates spontaneous and non-familiar stimuli-evoked neural activity.

Familiarity creates subjective memory of repeated innocuous experiences, reduces neural and behavioral responsiveness to those experiences, and enhances novelty detection. The neural correlates of the internal model of familiarity and the cellular mechanisms of enhanced novelty detection following multi-day repeated passive experience remain elusive. Using the mouse visual cortex as a model system, we test how the repeated passive experience of a 45° orientation-grating stimulus for multiple days alters spontaneous and non-familiar stimuli evoked neural activity in neurons tuned to familiar or non-familiar stimuli. We found that familiarity elicits stimulus competition such that stimulus selectivity reduces in neurons tuned to the familiar 45° stimulus; it increases in those tuned to the 90° stimulus but does not affect neurons tuned to the orthogonal 135° stimulus. Furthermore, neurons tuned to orientations 45° apart from the familiar stimulus dominate local functional connectivity. Interestingly, responsiveness to natural images, which consists of familiar and non-familiar orientations, increases subtly in neurons that exhibit stimulus competition. We also show the similarity between familiar grating stimulus-evoked and spontaneous activity increases, indicative of an internal model of altered experience.

Using pre-surgical suspicion to guide insula implantation strategy.

Rationale: Insular epilepsy can be a challenging diagnosis due to overlapping semiology and scalp EEG findings with frontal, temporal, and parietal lobe epilepsies. Stereotactic electroencephalography (sEEG) provides an opportunity to better localize seizure onset. The possibility of improved localization is balanced by implantation risk in this vascularly rich anatomic region. We review both safety and pre-implantation factors involved in insular electrode placement across four years at an academic medical center. Methods: Presurgical data, operative reports, and invasive EEG summaries were retrospectively reviewed for patients undergoing invasive epilepsy monitoring on the insula from 2016 through 2019. EEG reports were reviewed to record the presence of insula ictal and interictal involvement. We recorded which presurgical findings suggested insular involvement (insula lesion on MRI, insula changes on PET/SPECT/scalp EEG, characteristic semiology, or history of failed anterior temporal lobectomy). The likelihood of pre-sEEG insular onset was categorized as low suspicion if no presurgical findings were present ("rule out"), moderate suspicion if one finding was present, and high suspicion if two or more findings were present. Results: 76 patients received 189 insular electrodes as part of their implantation strategy for 79 surgical cases. Seven patients (8.9%) had insular ictal onset. One clinically significant complication (left hemiparesis) occurred in a patient with moderate suspicion for insular onset. There were 38 low suspicion cases, 36 moderate suspicion cases, and 5 high suspicion cases for pre-sEEG insula ictal onset. Two low suspicion (5.3%), three moderate suspicion (8.6%), and two high suspicion (40%) cases had insular ictal onset. Conclusions: The insula can safely receive sEEG. Having two or more presurgical factors indicating insular onset is a strong, albeit incomplete, predictor of insular seizure onset. Using pre-implantation clinical findings can offer clinicians predictive value for targeting the insula during invasive EEG monitoring.

Neurosurgery Resident Attrition Rates Defy Trends and Decrease During COVID-19 Pandemic.

OBJECTIVE: We sought to determine the effects of the coronavirus disease 2019 (COVID-19) pandemic on U.S. neurosurgery resident attrition. We report the changes in resident attrition due to transfers, withdrawal, or dismissal from program training during the COVID-19 pandemic. METHODS: Neurosurgery resident attrition data reported by the American Council of Graduate Medical Education for the academic year starting in July 2007 to the academic year ending in June 2022 were collected, and the rate of attrition was calculated. Individual postgraduate year program transfer rates were also calculated for the previous 7 consecutive academic years. The attrition rates for the academic years before the pandemic were compared with those during the pandemic. RESULTS: A total of 465 residents did not graduate from neurosurgical training during the past 15 academic years, of which 3 years were at least partially during the COVID-19 pandemic, resulting in a mean attrition rate of 2.5%. The attrition rates during the pandemic were lower than those before the pandemic (1.7% vs. 2.7%; P < 0.001), driven largely by a nearly twofold decrease in the withdrawal rate (0.67% vs. 1.2%; P = 0.003). Bivariate regression between the withdrawal and attrition rates showed a statistically significant correlation (r = 0.809; P < 0.001; r2 = 0.654). The first full year of the COVID-19 pandemic saw the most dramatic changes, with a z score for attrition of -1.9. Linear regression of the effect of training during the COVID-19 pandemic on attrition revealed a statistically significant difference (r = 0.563; P = 0.029; r2 = 0.317). The rate of withdrawal was most affected by training during the pandemic (r = 0.594; P = 0.010; r2 = 0.353). CONCLUSIONS: A statistically significant decline occurred in the rate of neurosurgery resident attrition during the COVID-19 pandemic that was most notable during the first full academic year (2020-2021). These findings were largely driven by a decrease in residents withdrawing from training programs. This contrasts with the overall trend toward resignation among healthcare workers during the pandemic. It is unclear what enduring ramifications this will have on neurosurgery residencies moving forward and whether we will see higher attrition rates as we transition toward a new normal. Future studies should examine trends in the attrition rates after the COVID-19 pandemic and determine the long-term effects of decreased attrition rates of residents during the pandemic.

Initial and corrective submovement encoding differences within primary motor cortex during precision reaching.

Precision reaching tasks often require corrective submovements for successful completion. Most studies of reaching have focused on single initial movements, and the cortical encoding model was implied to be the same for all submovements. However, corrective submovements may show different encoding patterns from the initial submovement with distinct patterns of activation across the population. Two rhesus macaques performed a precision center-out-task with small targets. Neural activity from single units in primary motor cortex and associated behavioral data were recorded to evaluate movement characteristics. Neural population data and individual neuronal firing rates identified with a peak finding algorithm to identify peaks in hand speed were examined for encoding differences between initial and corrective submovements. Individual neurons were fitted with a regression model that included the reach vector, position, and speed to predict firing rate. For both initial and corrective submovements, the largest effect remained movement direction. We observed a large subset changed their preferred direction greater than 45° between initial and corrective submovements. Neuronal depth of modulation also showed considerable variation when adjusted for movement speed. By utilizing principal component analysis, neural trajectories of initial and corrective submovements progressed through different neural subspaces. These findings all suggest that different neural encoding patterns exist for initial and corrective submovements within the cortex. We hypothesize that this variation in how neurons change to encode small, corrective submovements might allow for a larger portion of the neural space being used to encode a greater range of movements with varying amplitudes and levels of precision. New and Noteworthy: Neuronal recordings matched with kinematic behavior were collected in a precision center-out task that often required corrective movements. We reveal large differences in preferred direction and depth of modulation between initial and corrective submovements across the neural population. We then present a model of the neural population describing how these shifts in tuning create different subspaces for signaling initial and corrective movements likely to improve motor precision.

Repeated passive visual experience modulates spontaneous and non-familiar stimulievoked neural activity.

Familiarity creates subjective memory of repeated innocuous experiences, reduces neural and behavioral responsiveness to those experiences, and enhances novelty detection. The neural correlates of the internal model of familiarity and the cellular mechanisms of enhanced novelty detection following multi-day repeated passive experience remain elusive. Using the mouse visual cortex as a model system, we test how the repeated passive experience of a 45° orientation-grating stimulus for multiple days alters spontaneous and non-familiar stimuli evoked neural activity in neurons tuned to familiar or non-familiar stimuli. We found that familiarity elicits stimulus competition such that stimulus selectivity reduces in neurons tuned to the familiar 45° stimulus; it increases in those tuned to the 90° stimulus but does not affect neurons tuned to the orthogonal 135° stimulus. Furthermore, neurons tuned to orientations 45° apart from the familiar stimulus dominate local functional connectivity. Interestingly, responsiveness to natural images, which consists of familiar and non-familiar orientations, increases subtly in neurons that exhibit stimulus competition. We also show the similarity between familiar grating stimulus-evoked and spontaneous activity increases, indicative of an internal model of altered experience.

Excitation-inhibition imbalance disrupts visual familiarity in amyloid and non-pathology conditions.

Neuronal hyperactivity induces memory deficits in Alzheimer's disease. However, how hyperactivity disrupts memory is unclear. Using in vivo synaptic imaging in the mouse visual cortex, we show that structural excitatory-inhibitory synapse imbalance in the apical dendrites favors hyperactivity in early amyloidosis. Consistent with this, natural images elicit neuronal hyperactivity in these mice. Compensatory changes that maintain activity homeostasis disrupt functional connectivity and increase population sparseness such that a small fraction of neurons dominates population activity. These properties reduce the selectivity of neural response to natural images and render visual recognition memory vulnerable to interference. Deprivation of non-specific visual experiences improves the neural representation and behavioral expression of visual familiarity. In contrast, in non-pathological conditions, deprivation of non-specific visual experiences induces disinhibition, increases excitability, and disrupts visual familiarity. We show that disrupted familiarity occurs when the fraction of high-responsive neurons and the persistence of neural representation of a memory-associated stimulus are not constrained.

Evaluating Match and Attrition Rates for Women and African Americans in Neurosurgery.

BACKGROUND: Previous efforts to increase diversity in neurosurgery have been aimed primarily at female inclusion while little analysis of other under-represented groups has been performed. OBJECTIVE: To evaluate match and retention rates of under-represented groups in neurosurgery, specifically Black and female applicants compared with non-Black and male applicants. METHODS: Match lists, Electronic Residency Application Service data, and National Resident Matching Program data were retrospectively reviewed along with publicly available residency program information for successful matriculants from 2017 to 2020. Residents were classified into demographic groups, and analysis of match and retention rates was performed. RESULTS: For 1780 applicants from 2017 to 2020, 439 identified as female while 1341 identified as male. Of these 1780 applicants, 128 identified as Black and 1652 identified as non-Black. Male and female applicants matched at similar rates ( P = .76). Black applicants matched at a lower rate than non-Black applicants ( P < .001). From 2017 to 2020, neither race nor sex was associated with retention as 94.1% of male applicants and 93.2% of female applicants were retained ( P = .63). In total, 95.2% of Black residents and 93.9% of non-Black residents were retained ( P = .71). No intraregional or inter-regional differences in retention were found for any group. CONCLUSION: Although sex parity has improved, Black applicants match at lower rates than non-Black applicants but are retained after matriculation at similar rates. Neurosurgery continues to recruit fewer female applicants than male applicants. More work is needed to extend diversity to recruit under-represented applicants. Future studies should target yearly follow-up of retention and match rates to provide trends as a measure of diversification progress within the field.

Cortico-cortical drive in a coupled premotor-primary motor cortex dynamical system.

In the conventional view of sensorimotor control, the premotor cortex (PM) plans actions that are executed by the primary motor cortex (M1). This notion arises in part from many experiments that have imposed a preparatory "planning" period, during which PM becomes active without M1. But during many natural movements, PM and M1 are co-activated, making it difficult to distinguish their functional roles. We leverage coupled dynamical systems models (cDSMs) to uncover interactions between PM and M1 during movements performed with no preparatory period. We build cDSMs using neural and behavioral data recorded from two non-human primates as they performed a reach-grasp-manipulate task. PM and M1 interact dynamically throughout these movements. Whereas PM drives the M1 in some situations, in other situations, M1 drives PM activity, contrary to the conventional assumption. Our DSM framework provides additional predictions differentiating the roles of PM and M1 in controlling movement.

Source-sink connectivity: a novel interictal EEG marker for seizure localization.

Over 15 million epilepsy patients worldwide have drug-resistant epilepsy. Successful surgery is a standard of care treatment but can only be achieved through complete resection or disconnection of the epileptogenic zone, the brain region(s) where seizures originate. Surgical success rates vary between 20% and 80%, because no clinically validated biological markers of the epileptogenic zone exist. Localizing the epileptogenic zone is a costly and time-consuming process, which often requires days to weeks of intracranial EEG (iEEG) monitoring. Clinicians visually inspect iEEG data to identify abnormal activity on individual channels occurring immediately before seizures or spikes that occur interictally (i.e. between seizures). In the end, the clinical standard mainly relies on a small proportion of the iEEG data captured to assist in epileptogenic zone localization (minutes of seizure data versus days of recordings), missing opportunities to leverage these largely ignored interictal data to better diagnose and treat patients. IEEG offers a unique opportunity to observe epileptic cortical network dynamics but waiting for seizures increases patient risks associated with invasive monitoring. In this study, we aimed to leverage interictal iEEG data by developing a new network-based interictal iEEG marker of the epileptogenic zone. We hypothesized that when a patient is not clinically seizing, it is because the epileptogenic zone is inhibited by other regions. We developed an algorithm that identifies two groups of nodes from the interictal iEEG network: those that are continuously inhibiting a set of neighbouring nodes ('sources') and the inhibited nodes themselves ('sinks'). Specifically, patient-specific dynamical network models were estimated from minutes of iEEG and their connectivity properties revealed top sources and sinks in the network, with each node being quantified by source-sink metrics. We validated the algorithm in a retrospective analysis of 65 patients. The source-sink metrics identified epileptogenic regions with 73% accuracy and clinicians agreed with the algorithm in 93% of seizure-free patients. The algorithm was further validated by using the metrics of the annotated epileptogenic zone to predict surgical outcomes. The source-sink metrics predicted outcomes with an accuracy of 79% compared to an accuracy of 43% for clinicians' predictions (surgical success rate of this dataset). In failed outcomes, we identified brain regions with high metrics that were untreated. When compared with high frequency oscillations, the most commonly proposed interictal iEEG feature for epileptogenic zone localization, source-sink metrics outperformed in predictive power (by a factor of 1.2), suggesting they may be an interictal iEEG fingerprint of the epileptogenic zone.

Novel application of a force sensor during sit-to-stands to measure dynamic cerebral autoregulation onset.

Current sit-to-stand methods measuring dynamic cerebral autoregulation (dCA) do not capture the precise onset of the time delay (TD) response. Reduced sit-to-stand reactions in older adults and individuals post-stroke could inadvertently introduce variability, error, and imprecise timing. We applied a force sensor during a sit-to-stand task to more accurately determine how TD before the onset of dCA may be altered. Middle cerebral artery blood velocity (MCAv) and mean arterial pressure (MAP) were measured during two sit-to-stands separated by 15 min. Recordings started with participants sitting on a force-sensitive resistor for 60 s, then asked to stand for 2 min. Upon standing, the force sensor voltage immediately dropped and marked the exact moment of arise-and-off (AO). Time from AO until an increase in cerebrovascular conductance (CVC = MCAv/MAP) was calculated as TD. We tested the sensor in four healthy young adults, two older adults, and two individuals post-stroke. Healthy young adults stood quickly and the force sensor detected a small change in TD compared to classically estimated AO, from verbal command to stand. When compared to the estimated AO, older adults had a delayed measured AO and TD decreased up to ~53% while individuals post-stroke had an early AO and TD increased up to ~14%. The stance time during the sit-to-stand has the potential to influence the TD before the onset of dCA metric. As observed in the older adults and participants with stroke, this response may drastically vary and influence TD.

Cyclic, Condition-Independent Activity in Primary Motor Cortex Predicts Corrective Movement Behavior.

Reaching movements are known to have large condition-independent (CI) neural activity and cyclic neural dynamics. A new precision center-out task was performed by rhesus macaques to test the hypothesis that cyclic, CI neural activity in the primary motor cortex (M1) occurs not only during initial reaching movements but also during subsequent corrective movements. Corrective movements were observed to be discrete with time courses and bell-shaped speed profiles similar to the initial movements. CI cyclic neural trajectories were similar and repeated for initial and each additional corrective submovement. The phase of the cyclic CI neural activity predicted the time of peak movement speed more accurately than regression of instantaneous firing rate, even when the subject made multiple corrective movements. Rather than being controlled as continuations of the initial reach, a discrete cycle of motor cortex activity encodes each corrective submovement.

Condition-Dependent Neural Dimensions Progressively Shift during Reach to Grasp.

Neural population space analysis was performed to assess the dimensionality and dynamics of the neural population in the primary motor cortex (M1) during a reach-grasp-manipulation task in which both the reach location and the object being grasped were varied. We partitioned neural activity into three components: (1) general task-related activity independent of location and object, (2) location- and/or object-related activity, and (3) noise. Neural modulation related to location and/or object was only one-third the size of either general task modulation or noise. The neural dimensions of location and/or object-related activity overlapped with both the general task and noise dimensions. Rather than large amplitude modulation in a fixed set of dimensions, the active dimensions of location and/or object modulation shifted progressively over the time course of a trial.

Mirror Neuron Populations Represent Sequences of Behavioral Epochs During Both Execution and Observation.

Mirror neurons (MNs) have the distinguishing characteristic of modulating during both execution and observation of an action. Although most studies of MNs have focused on various features of the observed movement, MNs also may monitor the behavioral circumstances in which the movement is embedded, including time periods preceding and following the observed movement. Here, we recorded multiple MNs simultaneously from implanted electrode arrays as two male monkeys executed and observed a reach, grasp, and manipulate task involving different target objects. MNs were recorded from premotor cortex (PM-MNs) and primary motor cortex (M1-MNs). During execution trials, hidden Markov models (HMMs) applied to the activity of either PM-MN or M1-MN populations most often detected sequences of four hidden states, which we named according to the behavioral epoch during which each state began: initial, reaction, movement, and final. The hidden states of MN populations thus reflected not only the movement, but also three behavioral epochs during which no movement occurred. HMMs trained on execution trials could decode similar sequences of hidden states in observation trials, with complete hidden state sequences decoded more frequently from PM-MN populations than from M1-MN populations. Moreover, population trajectories projected in a 2D plane defined by execution trials were preserved in observation trials more for PM-MN than for M1-MN populations. These results suggest that MN populations represent entire behavioral sequences, including both movement and non-movement. PM-MN populations showed greater similarity than M1-MN populations in their representation of behavioral sequences during execution versus observation.SIGNIFICANCE STATEMENT Mirror neurons (MNs) are thought to provide a neural mechanism for understanding the actions of others. However, for an action to be understood, both the movement per se and the non-movement context before and after the movement need to be represented. We found that simultaneously recorded MN populations encoded sequential hidden neural states corresponding approximately to sequential behavioral epochs of a reach, grasp, and manipulate task. During observation trials, hidden state sequences were similar to those identified in execution trials. Hidden state similarity was stronger for MN populations in premotor cortex than for those in primary motor cortex. Execution/observation similarity of hidden state sequences may contribute to understanding the actions of others without actually performing the action oneself.