Control of working memory by phase-amplitude coupling of human hippocampal neurons.

Retaining information in working memory is a demanding process that relies on cognitive control to protect memoranda-specific persistent activity from interference1,2. However, how cognitive control regulates working memory storage is unclear. Here we show that interactions of frontal control and hippocampal persistent activity are coordinated by theta-gamma phase-amplitude coupling (TG-PAC). We recorded single neurons in the human medial temporal and frontal lobe while patients maintained multiple items in their working memory. In the hippocampus, TG-PAC was indicative of working memory load and quality. We identified cells that selectively spiked during nonlinear interactions of theta phase and gamma amplitude. The spike timing of these PAC neurons was coordinated with frontal theta activity when cognitive control demand was high. By introducing noise correlations with persistently active neurons in the hippocampus, PAC neurons shaped the geometry of the population code. This led to higher-fidelity representations of working memory content that were associated with improved behaviour. Our results support a multicomponent architecture of working memory1,2, with frontal control managing maintenance of working memory content in storage-related areas3-5. Within this framework, hippocampal TG-PAC integrates cognitive control and working memory storage across brain areas, thereby suggesting a potential mechanism for top-down control over sensory-driven processes.

Encoding of Predictive Associations in Human Prefrontal and Medial Temporal Neurons During Pavlovian Appetitive Conditioning.

Pavlovian conditioning is thought to involve the formation of learned associations between stimuli and values, and between stimuli and specific features of outcomes. Here, we leveraged human single neuron recordings in ventromedial prefrontal, dorsomedial frontal, hippocampus, and amygdala while patients of both sexes performed an appetitive Pavlovian conditioning task probing both stimulus-value and stimulus-stimulus associations. Ventromedial prefrontal cortex encoded predictive value along with the amygdala, and also encoded predictions about the identity of stimuli that would subsequently be presented, suggesting a role for neurons in this region in encoding predictive information beyond value. Unsigned error signals were found in dorsomedial frontal areas and hippocampus, potentially supporting learning of non-value related outcome features. Our findings implicate distinct human prefrontal and medial temporal neuronal populations in mediating predictive associations which could partially support model-based mechanisms during Pavlovian conditioning.

Properties and hemispheric differences of theta oscillations in the human hippocampus.

The left and right primate hippocampi (LH and RH) are thought to support distinct functions, but little is known about differences between the hemispheres at the neuronal level. We recorded single-neuron and local field potentials from the human hippocampus in epilepsy patients implanted with depth electrodes. We detected theta-frequency bouts of oscillatory activity while patients performed a visual recognition memory task. Theta appeared in bouts of 3.16 cycles, with sawtooth-shaped oscillations that had a prolonged downswing period. Outside the seizure onset zone, the average frequency of theta bouts was higher in the RH compared to the LH (6.0 vs. 5.3 Hz). LH theta bouts had lower amplitudes and a higher prevalence compared to the RH (26% vs. 21% of total time). Additionally, the RH contained a population of thin spiking visually tuned neurons that were not present in the LH. These data show that human theta appears in short oscillatory bouts whose properties vary between hemispheres, thereby revealing neurophysiological properties of the hippocampus that differ between the hemispheres.

Extent of Single-Neuron Activity Modulation by Hippocampal Interictal Discharges Predicts Declarative Memory Disruption in Humans.

Memory deficits are common in epilepsy patients. In these patients, the interictal EEG commonly shows interictal epileptiform discharges (IEDs). While IEDs are associated with transient cognitive impairments, it remains poorly understood why this is. We investigated the effects of human (male and female) hippocampal IEDs on single-neuron activity during a memory task in patients with medically refractory epilepsy undergoing depth electrode monitoring. We quantified the effects of hippocampal IEDs on single-neuron activity and the impact of this modulation on subjectively declared memory strength. Across all recorded neurons, the activity of 50 of 728 neurons were significantly modulated by IEDs, with the strongest modulation in the medial temporal lobe (33 of 416) and in particular the right hippocampus (12 of 58). Putative inhibitory neurons, as identified by their extracellular signature, were more likely to be modulated by IEDs than putative excitatory neurons (19 of 157 vs 31 of 571). Behaviorally, the occurrence of hippocampal IEDs was accompanied by a disruption of recognition of familiar images only if they occurred up to 2 s before stimulus onset. In contrast, IEDs did not impair encoding or recognition of novel images, indicating high temporal and task specificity of the effects of IEDs. The degree of modulation of individual neurons by an IED correlated with the declared confidence of a retrieval trial, with higher firing rates indicative of reduced confidence. Together, these data link the transient modulation of individual neurons by IEDs to specific declarative memory deficits in specific cell types, thereby revealing a mechanism by which IEDs disrupt medial temporal lobe-dependent declarative memory retrieval processes.SIGNIFICANCE STATEMENT Interictal epileptiform discharges (IEDs) are thought to be a cause of memory deficits in chronic epilepsy patients, but the underlying mechanisms are not understood. Utilizing single-neuron recordings in epilepsy patients, we found that hippocampal IEDs transiently change firing of hippocampal neurons and disrupted selectively the retrieval, but not encoding, of declarative memories. The extent of the modulation of the individual firing of hippocampal neurons by an IED predicted the extent of reduction of subjective retrieval confidence. Together, these data reveal a specific kind of transient cognitive impairment caused by IEDs and link this impairment to the modulation of the activity of individual neurons. Understanding the mechanisms by which IEDs impact memory is critical for understanding memory impairments in epilepsy patients.

Value-Related Neuronal Responses in the Human Amygdala during Observational Learning.

The amygdala plays an important role in many aspects of social cognition and reward learning. Here, we aimed to determine whether human amygdala neurons are involved in the computations necessary to implement learning through observation. We performed single-neuron recordings from the amygdalae of human neurosurgical patients (male and female) while they learned about the value of stimuli through observing the outcomes experienced by another agent interacting with those stimuli. We used a detailed computational modeling approach to describe patients' behavior in the task. We found a significant proportion of amygdala neurons whose activity correlated with both expected rewards for oneself and others, and in tracking outcome values received by oneself or other agents. Additionally, a population decoding analysis suggests the presence of information for both observed and experiential outcomes in the amygdala. Encoding and decoding analyses suggested observational value coding in amygdala neurons occurred in a different subset of neurons than experiential value coding. Collectively, these findings support a key role for the human amygdala in the computations underlying the capacity for learning through observation.SIGNIFICANCE STATEMENT Single-neuron studies of the human brain provide a unique window into the computational mechanisms of cognition. In this study, epilepsy patients implanted intracranially with hybrid depth electrodes performed an observational learning (OL) task. We measured single-neuron activity in the amygdala and found a representation for observational rewards as well as observational expected reward values. Additionally, distinct subsets of amygdala neurons represented self-experienced and observational values. This study provides a rare glimpse into the role of human amygdala neurons in social cognition.

Single-neuron correlate of epilepsy-related cognitive deficits in visual recognition memory in right mesial temporal lobe.

OBJECTIVE: Impaired memory is a common comorbidity of refractory temporal lobe epilepsy (TLE) and often perceived by patients as more problematic than the seizures themselves. The objective of this study is to understand what the relationship of these behavioral impairments is to the underlying pathophysiology, as there are currently no treatments for these deficits, and it remains unknown what circuits are affected. METHODS: We recorded single neurons in the medial temporal lobes (MTLs) of 62 patients (37 with refractory TLE) who performed a visual recognition memory task to characterize the relationship between behavior, tuning, and anatomical location of memory selective and visually selective neurons. RESULTS: Subjects with a seizure onset zone (SOZ) in the right but not left MTL demonstrated impaired ability to recollect as indicated by the degree of asymmetry of the receiver operating characteristic curve. Of the 1973 recorded neurons, 159 were memory selective (MS) and 366 were visually selective (VS) category cells. The responses of MS neurons located within right but not left MTL SOZs were impaired during high-confidence retrieval trials, mirroring the behavioral deficit seen both in our task and in standardized neuropsychological tests. In contrast, responses of VS neurons were unimpaired in both left and right MTL SOZs. Our findings show that neuronal dysfunction within SOZs in the MTL was specific to a functional cell type and behavior, whereas other cell types respond normally even within the SOZ. We show behavioral metrics that detect right MTL SOZ-related deficits and identify a neuronal correlate of this impairment. SIGNIFICANCE: Together, these findings show that single-cell responses can be used to assess the causal effects of local circuit disruption by an SOZ in the MTL, and establish a neural correlate of cognitive impairment due to epilepsy that can be used as a biomarker to assess the efficacy of novel treatments.

Pituitary society expert Delphi consensus: operative workflow in endoscopic transsphenoidal pituitary adenoma resection.

PURPOSE: Surgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice. METHODS: A mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached. RESULTS: There was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured. CONCLUSIONS: Through an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed "core" steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The "optional" steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world.

Abstract goal representation in visual search by neurons in the human pre-supplementary motor area.

The medial frontal cortex is important for goal-directed behaviours such as visual search. The pre-supplementary motor area (pre-SMA) plays a critical role in linking higher-level goals to actions, but little is known about the responses of individual cells in this area in humans. Pre-SMA dysfunction is thought to be a critical factor in the cognitive deficits that are observed in diseases such as Parkinson's disease and schizophrenia, making it important to develop a better mechanistic understanding of the pre-SMA's role in cognition. We simultaneously recorded single neurons in the human pre-SMA and eye movements while subjects performed goal-directed visual search tasks. We characterized two groups of neurons in the pre-SMA. First, 40% of neurons changed their firing rate whenever a fixation landed on the search target. These neurons responded to targets in an abstract manner across several conditions and tasks. Responses were invariant to motor output (i.e. button press or not), and to different ways of defining the search target (by instruction or pop-out). Second, ∼50% of neurons changed their response as a function of fixation order. Together, our results show that human pre-SMA neurons carry abstract signals during visual search that indicate whether a goal was reached in an action- and cue-independent manner. This suggests that the pre-SMA contributes to goal-directed behaviour by flexibly signalling goal detection and time elapsed since start of the search, and this process occurs regardless of task. These observations provide insights into how pre-SMA dysfunction might impact cognitive function.

Pituitary apoplexy associated with acute COVID-19 infection and pregnancy.

PURPOSE: We report a case of a pregnant female presenting with pituitary apoplexy and simultaneous SARS-CoV-2 infection with a focus on management decisions. CLINICAL HISTORY: A 28-year-old G5P1 38w1d female presented with 4 days of blurry vision, left dilated pupil, and headache. She tested positive for SARS-CoV-2 on routine nasal swab testing but denied cough or fever. Endocrine testing demonstrated an elevated serum prolactin level, and central hypothyroidism. MRI showed a cystic-solid lesion with a fluid level in the pituitary fossa and expansion of the sella consistent with pituitary apoplexy. Her visual symptoms improved with corticosteroid administration and surgery was delayed to two weeks after her initial COVID-19 infection and to allow for safe delivery of the child. A vaginal delivery under epidural anesthetic occurred at 39 weeks. Two days later, transsphenoidal resection of the mass was performed under strict COVID-19 precautions including use of Powered Air Purifying Respirators (PAPRs) and limited OR personnel given high risk of infection during endonasal procedures. Pathology demonstrated a liquefied hemorrhagic mass suggestive of pituitary apoplexy. She made a full recovery and was discharged home two days after surgery. CONCLUSION: Here we demonstrate the first known case of successful elective induction of vaginal delivery and transsphenoidal intervention in a near full term gravid patient presenting with pituitary apoplexy and acute SARS-CoV-2 infection. Further reports may help determine if there is a causal relationship or if these events are unrelated. Close adherence to guidelines for caregivers can greatly reduce risk of infection.

Trends in endoscopic and microscopic transsphenoidal surgery: a survey of the international society of pituitary surgeons between 2010 and 2020.

PURPOSE: This comparative survey of surgical practice patterns between 2010 and 2020 aims to elicit trends in practice patterns for transsphenoidal surgery and to identify areas for improvement. METHODS: Web-based surveys were sent to the International Society of Pituitary Surgeons via a membership listserv in 2010 and 2020. These 33-item surveys collected information on demographics, surgical approach, perceived advantages and disadvantages, and recommendations for improvements. Statistical analyses were conducted using the Mann-Whitney U test for continuous variables and Fisher's exact test for categorical variables. RESULTS: There were 51 respondents in 2010 and 82 respondents in 2020. The majority were full-time academic surgeons from the United States or Europe. Preference for a purely endoscopic technique increased from 43% in 2010 to 87% in 2020. Preference for routinely working with an otolaryngologist or second neurosurgeon increased from 35 to 51%. Most surgeons (74%) reported that they were more likely to achieve a greater extent of resection with the endoscope, though 51% noted increased operating time. The most commonly rated advantage (34%) of endoscopic TSS was fewer postoperative nasoseptal perforations; the most commonly (34%) rated disadvantage was more postoperative complications, including cerebrospinal fluid leak. Respondents were divided on whether microscopic TSS should continue to be taught in residency. Many (32%) advocated for improved endoscopic instrumentation and team training. CONCLUSION: Endoscopic TSS is now the clearly preferred method for surgery amongst a cohort of higher-volume academic neurosurgeons. This trend is likely to continue, and this provides guidelines for future training.

Working Memory Load-related Theta Power Decreases in Dorsolateral Prefrontal Cortex Predict Individual Differences in Performance.

Holding information in working memory (WM) is an active and effortful process that is accompanied by sustained load-dependent changes in oscillatory brain activity. These proportional power increases are often reported in EEG studies recording theta over frontal midline sites. Intracranial recordings, however, yield mixed results, depending on the brain area being recorded from. We recorded intracranial EEG with depth electrodes in 13 patients with epilepsy who were performing a Sternberg WM task. Here, we investigated patterns of theta power changes as a function of memory load during maintenance in three areas critical for WM: dorsolateral prefrontal cortex (DLPFC), dorsal ACC (dACC), and hippocampus. Theta frequency power in both hippocampus and dACC increased during maintenance. In contrast, theta frequency power in the DLPFC decreased during maintenance, and this decrease was proportional to memory load. Only the power decreases in DLPFC, but not the power increases in hippocampus and dACC, were predictive of behavior in a given trial. The extent of the load-related theta power decreases in the DLPFC in a given participant predicted a participant's RTs, revealing that DLPFC theta explains individual differences in WM ability between participants. Together, these data reveal a pattern of theta power decreases in the DLPFC that is predictive of behavior and that is opposite of that in other brain areas. This result suggests that theta band power changes serve different cognitive functions in different brain areas and specifically that theta power decreases in DLPFC have an important role in maintenance of information.

Sustained quality-of-life improvements over 10 years after deep brain stimulation for dystonia.

BACKGROUND: Little is known about the quality of life of people with dystonia and DBS beyond 5 years. The objectives of this study were (1) to examine the long-term quality-of-life outcomes in a large cohort of people with dystonia and DBS, (2) to determine the incidence of stimulation-induced parkinsonism, and (3) to elucidate the potential long-term cognitive impact of DBS in this cohort. METHODS: Fifty-four subjects with dystonia and DBS for more than 5 years were contacted via social media and were offered to complete a quality-of-life survey comparing current-day life and life prior to DBS. The primary study outcomes were the Short Form survey, a parkinsonian symptoms questionnaire, the Telephone Montreal Cognitive Assessment, and the Measurement of Every Day Cognition. RESULTS: Thirty-seven of 54 subjects consented to the study. Average age was 39.7 ± 16.6 years, 16 were female, and 23 were DYT1+. Average time from implantation was 10.5 years. Average total Short Form survey scores improved, from 43.7 pre-DBS to 69.5 current day (P < 0.0005). Mean total self-reported parkinsonian symptom score was 13.8 ± 14.7, with worsening balance and hypophonia the most common. Average Telephone Montreal Cognitive Assessment was 20.1 ± 1.6, with 3 of 29 scores (10.3%) in the impaired range (score of 18 or less). Average total Every Day Cognition score was 1.25 ± 0.35, with 3 subjects (10.3%) scoring in the range of impaired cognition (>1.81). CONCLUSIONS: DBS for dystonia results in long-term quality-of-life improvements that persist on average 10 years or more after surgery. The prevalence of stimulation-induced parkinsonism and cognitive impairment is low. © 2018 International Parkinson and Movement Disorder Society.

Consensus-driven in-hospital cortisol assessment after ACTH-secreting pituitary adenoma resection.

PURPOSE: Remission from Cushing disease (CD) after pituitary adenoma resection may be predicted by a postoperative reduction in serum cortisol level. A 2008 consensus statement recommends assessing morning cortisol levels during the first postoperative week, and replacing glucocorticoid (GC) if cortisol nadir of < 2 or < 5 µg/dL is achieved. We sought to evaluate adherence to consensus recommendations following adrenocorticotropic hormone (ACTH)-secreting pituitary adenoma resection at our tertiary medical center, and assess time to cortisol nadir to better define the window for assessment and intervention. METHODS: We retrospectively analyzed data extracted from in-hospital electronic medical records for CD surgeries between January 1991 and September 2015. We compared cortisol levels and collection times, ACTH measurement, and postoperative and discharge GC treatment before and after consensus statement publication in July 2008. RESULTS: 107 surgeries were performed in 92 patients with CD. After 2008, more surgeries had at least one cortisol value assessed (67.9% before vs. 91.3% after, p = 0.033), with median initial cortisol measurement at 14 h post-surgery. However, ACTH measurement remained unchanged (42.9% vs. 43.5%; p > 0.99). Cortisol collection during GC treatment tended to increase (32.7% vs. 57.1%; p = 0.068). Of surgeries performed without prior GC treatment, 31.7 and 55.0% had a cortisol nadir of < 2 and < 5 µg/dL, respectively, within 72 h postoperative. CONCLUSIONS: Our physicians were more diligent in measuring in-hospital postoperative cortisol levels consistent with 2008 consensus recommendations. Better management of cortisol measurements and their timing is an opportunity for improvement.

Safety and Utility of Hybrid Depth Electrodes for Seizure Localization and Single-Unit Neuronal Recording.

BACKGROUND: Invasive electrode monitoring provides more precise localization of epileptogenic foci in patients with medically refractory epilepsy. The use of hybrid depth electrodes that include microwires for simultaneous single-neuron monitoring is becoming more widespread. OBJECTIVE: To determine the safety and utility of hybrid depth electrodes for intracranial monitoring of medically refractory epilepsy. METHODS: We reviewed the medical charts of 53 cases of medically refractory epilepsy operated on from 2006 to 2017, where both non-hybrid and hybrid microwire depth electrodes were used for intracranial monitoring. We assessed the localization accuracy and complications that arose to assess the relative safety and utility of hybrid depth electrodes compared with standard electrodes. RESULTS: A total of 555 electrodes were implanted in 52 patients. The overall per-electrode complication rate was 2.3%, with a per-case complication rate of 20.8%. There were no infections or deaths. Serious or hemorrhagic complications occurred in 2 patients (0.4% per-electrode risk). Complications did not correlate with the use of any particular electrode type, and hybrids were equally as reliable as standard electrodes in localizing seizure onset zones. CONCLUSIONS: Hybrid depth electrodes appear to be as safe and effective as standard depth electrodes for intracranial monitoring and provide unique opportunities to study the human brain at single-neuron resolution.

Neurons in the human amygdala selective for perceived emotion.

The human amygdala plays a key role in recognizing facial emotions and neurons in the monkey and human amygdala respond to the emotional expression of faces. However, it remains unknown whether these responses are driven primarily by properties of the stimulus or by the perceptual judgments of the perceiver. We investigated these questions by recording from over 200 single neurons in the amygdalae of 7 neurosurgical patients with implanted depth electrodes. We presented degraded fear and happy faces and asked subjects to discriminate their emotion by button press. During trials where subjects responded correctly, we found neurons that distinguished fear vs. happy emotions as expressed by the displayed faces. During incorrect trials, these neurons indicated the patients' subjective judgment. Additional analysis revealed that, on average, all neuronal responses were modulated most by increases or decreases in response to happy faces, and driven predominantly by judgments about the eye region of the face stimuli. Following the same analyses, we showed that hippocampal neurons, unlike amygdala neurons, only encoded emotions but not subjective judgment. Our results suggest that the amygdala specifically encodes the subjective judgment of emotional faces, but that it plays less of a role in simply encoding aspects of the image array. The conscious percept of the emotion shown in a face may thus arise from interactions between the amygdala and its connections within a distributed cortical network, a scheme also consistent with the long response latencies observed in human amygdala recordings.

Human memory strength is predicted by theta-frequency phase-locking of single neurons.

Learning from novel experiences is a major task of the central nervous system. In mammals, the medial temporal lobe is crucial for this rapid form of learning. The modification of synapses and neuronal circuits through plasticity is thought to underlie memory formation. The induction of synaptic plasticity is favoured by coordinated action-potential timing across populations of neurons. Such coordinated activity of neural populations can give rise to oscillations of different frequencies, recorded in local field potentials. Brain oscillations in the theta frequency range (3-8 Hz) are often associated with the favourable induction of synaptic plasticity as well as behavioural memory. Here we report the activity of single neurons recorded together with the local field potential in humans engaged in a learning task. We show that successful memory formation in humans is predicted by a tight coordination of spike timing with the local theta oscillation. More stereotyped spiking predicts better memory, as indicated by higher retrieval confidence reported by subjects. These findings provide a link between the known modulation of theta oscillations by many memory-modulating behaviours and circuit mechanisms of plasticity.

Surgical management of pituicytomas: case series and comprehensive literature review.

OBJECTIVE: Pituicytomas are rare neoplasms that typically present as solid, noninfiltrative tumors occupying the sella and/or suprasellar space for which there is no consensus on optimal surgical management. We aimed to define a preferred surgical strategy for these tumors based on our clinical experience and comprehensive review of the world literature. DESIGN: Case series and review of the literature. METHODS: We documented the clinical, radiographic, and surgical findings of three patients with pituicytoma treated at our institution, as well as complications and long-term outcomes. A comprehensive review of the medical literature identified all cases of pituicytoma for which data regarding surgical approach, outcome and complications could be extracted. We compared our results with published data. RESULTS: All three cases at our institution achieved gross total removal. Two patients underwent an expanded endoscopic endonasal transsphenoidal and transplanum (EETS-TP) approach, while one tumor was removed via craniotomy. Post-operatively all patients developed pan-hypopitutarism. The patient undergoing craniotomy suffered profound visual loss but no other neurological complications were noted. A literature review identified 67 reported cases of pituicytoma. Surgical data was available in 60 cases. Surgical approach was documented in 57 patients. Sixty-three surgeries were performed in which approach and extent of resection was available. Gross total removal was obtained in 33 % of craniotomies, 42 % of transsphenoidal procedures, and 100 % of expanded transsphenoidal procedures. Neurological complications including visual loss, hemiparesis and cranial nerve palsies were reported after craniotomy, but not after transsphenoidal approaches. Overall EETS-TP approaches were associated with the highest rate of gross total removal and no visual or neurological complications. CONCLUSIONS: EETS-TP surgery is the preferred strategy for surgical removal of pituicytoma. EETS-TP and transsphenoidal approaches are associated with higher rates of gross total removal and lower rates of neurological complications than craniotomy. Gross total removal should be the intended goal of surgery.

Transsphenoidal surgery using a high definition video telescope for pituitary adenomas in dogs with pituitary dependent hypercortisolism: methods and results.

OBJECTIVE: To (1) establish a technique for transsphenoidal removal of pituitary adenomas in dogs with pituitary dependent hypercortisolism (PDH) using a high definition video telescope, and (2) report initial outcomes. STUDY DESIGN: Prospective case series. ANIMALS: Dogs with pituitary dependent hypercortisolism (PDH; n = 26) with suprasellar masses. METHODS: Pituitary tumors were removed using a modification of a transoral transsphenoidal approach. Surgery was observed using a high definition video telescope (VITOM™) and localization of the sella was performed by drilling pilot holes in the basisphenoid bone followed by computed tomography (CT). RESULTS: Dogs had PDH confirmed by urinary cortisol to creatinine ratio (UCCR) and endogenous ACTH assays, and tumors confirmed by MRI. There were no postoperative cerebrospinal fluid leaks, wound dehiscence, or surgical site infections. Overall postoperative mortality was 19% with no mortality observed in the last 16 dogs, indicating an initial "learning curve" followed by good surgical results. All dogs that survived the immediate postoperative period (1 week) returned to their owners in good health, on hormonal replacement therapy. Follow-up ranged from 3 to 36 months. Sustained tumor control and hormonal remission based on normalized ACTH and UCCR measurements were observed in 20/21 (95%) dogs at 1-year follow-up. CONCLUSIONS: Modifications of a trans-oral transsphenoidal technique for surgical removal of pituitary tumors provides a safe and effective strategy for long-term remission of PDH with acceptable morbidity and mortality.

Dataset of human-single neuron activity during a Sternberg working memory task.

We present a dataset of 1809 single neurons recorded from the human medial temporal lobe (amygdala and hippocampus) and medial frontal lobe (anterior cingulate cortex, pre-supplementary motor area, ventral medial prefrontal cortex) across 41 sessions from 21 patients that underwent seizure monitoring with depth electrodes. Subjects performed a screening task (907 neurons) to identify images for which highly selective cells were present. Subjects then performed a working memory task (902 neurons), in which they were sequentially presented with 1-3 images for which highly selective cells were present and, following a maintenance period, were asked if the probe was identical to one of the maintained images. This Neurodata Without Borders formatted dataset includes spike times, extracellular spike waveforms, stimuli presented, behavior, electrode locations, and subject demographics. As validation, we replicate previous findings on the selectivity of concept cells and their persistent activity during working memory maintenance. This large dataset of rare human single-neuron recordings and behavior enables the investigation of the neural mechanisms of working memory in humans.

Spontaneous sphenoid sinus meningocele with associated amenorrhea and headache: illustrative case.

BACKGROUND: Developmental meningoceles of the sphenoid sinus are uncommon. When encountered, they are often associated with cerebrospinal fluid (CSF) rhinorrhea. OBSERVATIONS: The authors present the case of a 27-year-old female with a large meningocele eroding through the sella turcica and sphenoid sinus into the nasopharynx. The patient presented with intractable headaches and amenorrhea without CSF rhinorrhea. LESSONS: The patient underwent an endoscopic endonasal transsphenoidal reduction of the meningocele with reelevation of the pituitary gland and skull base reconstruction with abdominal fat graft and nasoseptal flap.