Single neurons in the human medial temporal lobe flexibly shift representations across spatial and memory tasks.

Investigations into how individual neurons encode behavioral variables of interest have revealed specific representations in single neurons, such as place and object cells, as well as a wide range of cells with conjunctive encodings or mixed selectivity. However, as most experiments examine neural activity within individual tasks, it is currently unclear if and how neural representations change across different task contexts. Within this discussion, the medial temporal lobe is particularly salient, as it is known to be important for multiple behaviors including spatial navigation and memory, however the relationship between these functions is currently unclear. Here, to investigate how representations in single neurons vary across different task contexts in the medial temporal lobe, we collected and analyzed single-neuron activity from human participants as they completed a paired-task session consisting of a passive-viewing visual working memory and a spatial navigation and memory task. Five patients contributed 22 paired-task sessions, which were spike sorted together to allow for the same putative single neurons to be compared between the different tasks. Within each task, we replicated concept-related activations in the working memory task, as well as target-location and serial-position responsive cells in the navigation task. When comparing neuronal activity between tasks, we first established that a significant number of neurons maintained the same kind of representation, responding to stimuli presentations across tasks. Further, we found cells that changed the nature of their representation across tasks, including a significant number of cells that were stimulus responsive in the working memory task that responded to serial position in the spatial task. Overall, our results support a flexible encoding of multiple, distinct aspects of different tasks by single neurons in the human medial temporal lobe, whereby some individual neurons change the nature of their feature coding between task contexts.

A neuronal social trait space for first impressions in the human amygdala and hippocampus.

People instantaneously evaluate faces with significant agreement on evaluations of social traits. However, the neural basis for such rapid spontaneous face evaluation remains largely unknown. Here, we recorded from 490 neurons in the human amygdala and hippocampus and found that the neuronal activity was associated with the geometry of a social trait space. We further investigated the temporal evolution and modulation on the social trait representation, and we employed encoding and decoding models to reveal the critical social traits for the trait space. We also recorded from another 938 neurons and replicated our findings using different social traits. Together, our results suggest that there exists a neuronal population code for a comprehensive social trait space in the human amygdala and hippocampus that underlies spontaneous first impressions. Changes in such neuronal social trait space may have implications for the abnormal processing of social information observed in some neurological and psychiatric disorders.

Functional and resting-state characterizations of a periventricular heterotopic nodule associated with epileptogenic activity.

The object of this study was to extensively characterize a region of periventricular nodular heterotopia (PVNH) in an epilepsy patient to reveal its possible neurocognitive functional role(s). The authors used 3-T MRI approaches to exhaustively characterize a single, right hemisphere heterotopion in a high-functioning adult male with medically responsive epilepsy, which had manifested during late adolescence. The heterotopion proved to be spectroscopically consistent with a cortical-like composition and was interconnected with nearby ipsilateral cortical fundi, as revealed by fiber tractography (diffusion-weighted imaging) and resting-state functional connectivity MRI (rsfMRI). Moreover, the region of PVNH demonstrated two novel characterizations for a heterotopion. First, functional MRI (fMRI), as distinct from rsfMRI, showed that the heterotopion was significantly modulated while the patient watched animated video scenes of biological motion (i.e., cartoons). Second, rsfMRI, which demonstrated correlated brain activity during a task-negative state, uniquely showed directionality within an interconnected network, receiving positive path effects from patent cortical and cerebellar foci while outputting only negative path effects to specific brain foci.These findings are addressed in the context of the impact on noninvasive presurgical brain mapping strategies for adult and pediatric patient workups, as well as the impact of this study on an understanding of the functional cortical architecture underlying cognition from a neurodiversity and evolutionary perspective.

A Randomized Trial of Complications of Peripherally and Centrally Inserted Central Lines in the Neuro-Intensive Care Unit: Results of the NSPVC Trial.

OBJECTIVE: The objective of this study was to compare the relative number of complications from peripherally inserted central venous catheters (PICC) and centrally inserted central venous catheters (CVC) in the neuroscience intensive care unit (NSICU). METHODS: This study was carried out in a 32-bed NSICU in a large academic hospital in the USA from July 2015 until January 2017. Patients admitted requiring central venous access were randomly assigned to have a PICC or CVC inserted. Complications were recorded and compared. The primary outcome was all complications as well as combined numbers of large vein thrombosis, central-line-associated blood stream infections, and insertional trauma. Outcomes were compared using the Fisher's exact test, logistic regression, or unpaired T tests, as appropriate. RESULTS: One hundred and fifty-two patients were enrolled; 72 were randomized to the PICC arm and 80 to the CVC arm. There were no crossovers, withdrawals, nor losses to follow-up. The study was stopped at the second pre-planned interim analysis for futility. The combined number of large vein thrombosis, central-line-associated blood stream infection, and insertional trauma was 4/72 in the PICC arm and 1/80 in the CVC group (OR 4.6 (95% CI 0.5-42.6) p = 0.14). The number of all complications in the PICC arm was 14/72 compared to 10/80 in the CVC arm (OR 1.7 (95% CI 0.7-4.1) p = 0.24). CONCLUSIONS: PICCs and CVCs have similar numbers of complications when placed in patients admitted to the NSICU.

Deep Brain Stimulation for Multiple Sclerosis Tremor: A Meta-Analysis.

OBJECTIVES: To examine the effect of deep brain stimulation (DBS) on multiple sclerosis (MS)-tremor, as measured by a normalized scale of tremor severity, with a meta-analysis of the published literature. METHODS: Medline and EBSCO Host (January, 1998 to June, 2018) were systematically reviewed with librarian guidance, using the keywords "Deep brain stimulation" and "multiple sclerosis." Bibliographies and experts in the field were also consulted to identify missed articles. All therapeutic studies on DBS for MS-tremor, reported in the English language, within the study period were included. Papers that reported outcomes without a measure of central tendency and/or distribution were excluded. The papers were read in their entirety and graded for risk of bias according to the American Academy of Neurology (AAN) standards. To maximize statistical power, papers using different stimulation targets were grouped together. Outcomes were reported with the Fahn-Tolosa-Marin scale (FTM), the Bain-Finchley scale (CRS) and 3- and 4-point tremor severity scales and normalized with a Hedges g. RESULTS: The search produced 13 studies suitable for meta-analysis. The random-effects meta-analysis showed that DBS improved the Hedges standardized mean tremor score by 2.86 (95%CI 2.03-3.70, p < .00001). Heterogeneity was high, with an I2 of 84%, suggesting that random effects model is more appropriate. Adverse event rates varied from 8% to 50%. CONCLUSIONS: This meta-analysis provides level III evidence that DBS may improve MS-related tremor as measured by standardized tremor severity scales.

Utilizing neuronavigation for virtual electrode representation and safe resection following SEEG; a technical report.

Purpose: One of the most effective treatments for epilepsy is resection, but it remains underutilized. Efforts must be made to increase the ease, safety, and efficacy of epilepsy resection to improve utilization. Studies have shown an improved risk profile of stereoelectroencephalography (SEEG) over subdural grids (SDG) for invasive monitoring. One limitation to increased adoption of SEEG at epilepsy centers is the theoretical difficulty of planning a delayed resection once electrodes are removed. Our objective was to develop and present a technique using readily available neuronavigation technology to guide a cortical, non-lesional epilepsy resection with co-registration of imaging during invasive monitoring to imaging in an explanted patient, allowing for virtual visualization of electrodes. Methods: An example case taking advantage of the technique described above as an adjunct for an anatomically guided resection is presented with technical details and images. Results: Intraoperative neuronavigation was successfully used to virtually represent previously removed SEEG electrodes and accuracy could be easily verified by examining scars on the scalp, bone, dura and pia. Conclusions: The simple technique presented can be a useful adjunct to resection following SEEG. This may help increase the adoption of SEEG, even when resection is planned.

The use of custom 3D printed stereotactic frames for laser interstitial thermal ablation: technical note.

Over the last several years, laser interstitial thermotherapy (LITT) has gained wide acceptance for the treatment of a myriad of cranial lesions. A wide variety of techniques for placement of the laser fiber have been reported with a spectrum of perceived benefits and drawbacks. The authors present the first report of a customized 3D printed stereotactic frame for LITT. Approximately 1 week prior to surgery, 3-4 skull fiducials were placed after each of 5 patients received a local anesthetic as an outpatient. Radiographs with these fiducials were then used to create a trajectory to the lesion that would be treated with LITT. After the plan was completed, software was used to render a customized frame. On the day of surgery, the frame was attached to the implanted skull fiducials and the LITT catheter was placed. This procedure was carried out in 5 consecutive patients. In 2 patients, a needle biopsy was also performed. Intraoperative and postoperative imaging studies confirmed the accurate placement of the LITT catheter and the lesion created. Mean operating room time for all patients was 45 minutes but only 26 minutes when excluding the cases in which a biopsy was performed. To the best of the authors' knowledge, this is the first report of the use of a specific system, the STarFix microTargeting system, for use with LITT and brain biopsy. This system offers several advantages including fast operating times, extensive preoperative planning, no need for cranial fixation, and no need for frame or fiducial placement on the day of surgery. The accuracy of the system combined with these advantages may make this a preferred stereotactic method for LITT, especially in centers where LITT is performed in a diagnostic MRI suite.

Spinal Cord Stimulation for the Treatment of Neuropathic Pain Associated With Leprosy: A Case Report.

BACKGROUND: Leprosy is a major source of nerve damage and may lead to neuropathic pain as well as complex regional pain syndrome (CRPS). Spinal cord stimulation is an effective treatment for CRPS, but there are no reports of this treatment in a patient with leprosy. CASE PRESENTATION: The patient is a 55-year-old man who presented with CRPS in the arms and legs secondary to leprosy that persisted despite multidrug therapy, steroid treatment, and intravenous immunoglobulin. His pain and opioid use were both decreased with insertion of cervical and thoracic spinal cord stimulators. CONCLUSION: Spinal cord stimulation may be a valuable intervention for patients with leprosy-induced CRPS.

Life and Death 2: The First Neurosurgical Computer Simulation.

SUMMARY STATEMENT: Life and Death 2: The Brain was the first computerized neurosurgical simulator. It was developed as a commercial video game for a general audience. Despite this, it contains many valuable lessons for the simulation and education of nontechnical skills as well as being a historical landmark in the field of neurosurgery and medical simulation.

Continuous Intrathecal Medication Delivery With the IRRA flow Catheter: Pearls and Early Experience.

BACKGROUND AND OBJECTIVES: Intrathecal (IT) medications are routinely introduced through catheterization of the intraventricular space or subarachnoid space. There has been sporadic use of IT medications delivered directly to the ventricle either by intermittent injection through an external ventricular drain (EVD) or by an Ommaya reservoir with a ventricular catheter. IT medication delivery through EVD has many drawbacks, including the necessary opening of a sterile system, delivery of medication in a bolus form, and requirements to clamp the EVD after medication delivery. Despite these setbacks, IT medications delivered through EVD have been used across a wide range of applications, including antibiotic delivery treatment of vasospasm with nicardipine and delivery of tissue plasminogen activator. METHODS: We used a newly developed active fluid exchange device to treat various severe conditions involved in the cerebral ventricles. Here, we present our treatment protocols and advice on the techniques related to successful active fluid exchange therapy. RESULTS: Seventy patients have been treated with our system with various conditions, including subarachnoid hemorrhage, intraventricular hemorrhage, ventriculitis, and cerebral abscess. Total complication rate was 14% with only 1 catheter occlusion and low rates of hemorrhage, infection, and spinal fluid leak. CONCLUSION: Current continuous IT medication dosages and protocols are based on reports and consensus statements evaluating intermittent instillation of medication boluses. The pharmacokinetics of continuous dosing and the therapeutic and safety profiles of the medications need to be studied in a prospective manner to evaluate the true optimal dosing standards. Furthermore, the ability to deliver continuous, sterile medications directly through an IT route will open new avenues of pharmacotherapy that were previously closed. This report serves as a basic guide for the safe and effective use of the IRRA flow active fluid exchange catheter to deliver IT medications.

Neural mechanisms of face familiarity and learning in the human amygdala and hippocampus.

Recognizing familiar faces and learning new faces play an important role in social cognition. However, the underlying neural computational mechanisms remain unclear. Here, we record from single neurons in the human amygdala and hippocampus and find a greater neuronal representational distance between pairs of familiar faces than unfamiliar faces, suggesting that neural representations for familiar faces are more distinct. Representational distance increases with exposures to the same identity, suggesting that neural face representations are sharpened with learning and familiarization. Furthermore, representational distance is positively correlated with visual dissimilarity between faces, and exposure to visually similar faces increases representational distance, thus sharpening neural representations. Finally, we construct a computational model that demonstrates an increase in the representational distance of artificial units with training. Together, our results suggest that the neuronal population geometry, quantified by the representational distance, encodes face familiarity, similarity, and learning, forming the basis of face recognition and memory.

An International, Multicenter Feasibility Study on Active and Continuous Irrigation With Cerebrospinal Fluid Exchange for Improving Outcomes in Cerebral Ventriculitis.

BACKGROUND AND OBJECTIVES: Cerebral ventriculitis remains a challenging neurosurgical condition because of poor outcomes including mortality rates of nearly 80% and a prolonged course of treatment in survivors. Despite current conventional management, outcomes in some cases remain unsatisfactory, with no definitive therapeutic guidelines. This feasibility study aims to explore the use of a novel active, continuous irrigation and drainage system (IRRAflow [IRRAS AB]) combined with intraventricular drug delivery for patients with cerebral ventriculitis. METHODS: We conducted a multicenter, international, retrospective study of patients with ventriculitis who were treated with use of the IRRAflow system. Data collected included patient demographics, comorbidities, admission Glasgow Coma Scale score, baseline modified Rankin Scale (mRS) score, and imaging findings. Catheter occlusions, infections, and shunt placement were recorded for outcome assessment, along with discharge mRS scores and in-hospital deaths. RESULTS: Four centers contributed data for a total of 21 patients who had IRRAflow placement for treatment of ventriculitis. Thirteen (61.9%) were men (mean age = 49.8 ± 14.87 years). The median baseline mRS score was 1. The median Glasgow Coma Scale score at admission was 13. The etiology of ventriculitis was iatrogenic in 12 (57.1%) patients and secondary to an abscess in 9 (42.9%). No cases reported hemorrhage or failure of IRRAflow placement. Antibiotics were administered through the IRRAflow system in 13 (61.9%) cases in addition to systemic dosing. Sixteen (76.2%) patients had significant clinical improvement and resolution of ventriculitis. Seven (33.3%) patients required shunt placement after resolution because of persistent hydrocephalus. There were 6 (28.6%) in-hospital deaths. CONCLUSION: The use of active irrigation with drainage for continuous delivery of intraventricular irrigation fluid with antibiotics led to dramatically low mortality. In our case series, it led to a marked improvement in neurological status, imaging findings, and cerebrospinal fluid profiles, making it a technically feasible and safe treatment for ventriculitis.

Cognitive outcomes following unilateral magnetic resonance-guided focused ultrasound thalamotomy for essential tremor: findings from two cohorts.

Magnetic resonance-guided, focused ultrasound thalamotomy is a neurosurgical treatment for refractory essential tremor. This study examined cognitive outcomes following unilateral magnetic resonance-guided, focused ultrasound thalamotomy, targeting the ventral intermediate nucleus of the thalamus for essential tremor. The research was conducted at two sites: Sunnybrook Research Institute in Toronto, Canada, and West Virginia University School of Medicine Rockefeller Neuroscience Institute in West Virginia, USA. The study focused on cognitive changes at both the group and individual levels. Patients with refractory essential tremor completed cognitive testing before and after magnetic resonance-guided, focused ultrasound thalamotomy at both sites. The cognitive testing assessed domains of attention, processing speed, working memory, executive function, language and learning/memory. Postoperative changes in cognition were examined using paired t-tests and Wilcoxon signed-rank tests, as appropriate. Reliable change indices were calculated to assess clinically significant changes at the individual level. A total of 33 patients from Toronto and 22 patients from West Virginia were included. Following magnetic resonance-guided, focused ultrasound thalamotomy, there was a significant reduction in tremor severity in both cohorts. At the group level, there were no significant declines in postoperative cognitive performance in either cohort. The reliable change analyses revealed some variability at the individual level, with most patients maintaining stable performance or showing improvement. Taken together, the results from these two independent cohorts demonstrate that unilateral magnetic resonance-guided, focused ultrasound thalamotomy significantly reduces tremor severity without negatively impacting cognition at both the group and individual levels, highlighting the cognitive safety of magnetic resonance-guided focused ultrasound thalamotomy for essential tremor.

Traumatic brain injury in college students and the influence of alcohol consumption: A retrospective review from a rural state.

Objectives: There is a strong association between alcohol consumption and traumatic brain injury (TBI). Students are known to consume alcohol at a high rate. Despite the connection between alcohol and TBI, this is one of few studies to examine the connection between students, alcohol, and TBI. The objective of this study was to explore the relationship between students, alcohol, and TBI. Materials and Methods: A retrospective chart review utilizing the institutional trauma data back was performed for patients 18-26 years of age, admitted to the emergency department with a diagnosis of a TBI and positive blood alcohol. Patient diagnosis, injury mechanism, alcohol level on admission, urine drug screen, mortality, injury severity score, and discharge disposition were recorded. The data were analyzed using Wilcoxon rank-sum tests and Chi-square tests to identify differences between students and non-student groups. Results: Six hundred and thirty-six charts were reviewed for patients aged 18-26 with a positive blood alcohol level and TBI. The sample included 186 students, 209 non-students, and 241 uncertain of status. The student group had significantly higher levels of alcohol than the non-student group (P < 0.0001). P < 0.0001 showed that overall alcohol levels for males are significantly higher than levels of alcohol for females in the student group. Conclusion: Alcohol consumption contributes to significant injuries such as TBI in college students. Male students had a higher prevalence of TBI, and higher alcohol levels than female students. These results can be used to inform and better target harm reduction and alcohol awareness programs.

Outpatient Deep Brain Stimulation Surgery Is a Safe Alternative to Inpatient Admission.

BACKGROUND: Deep brain stimulation (DBS) is usually performed as an inpatient procedure. The COVID-19 pandemic effected a practice change at our institution with outpatient DBS performed because of limited inpatient and surgical resources. Although this alleviated use of hospital resources, the comparative safety of outpatient DBS surgery is unclear. OBJECTIVE: To compare the safety and incidence of early postoperative complications in patients undergoing DBS procedures in the outpatient vs inpatient setting. METHODS: We retrospectively reviewed all outpatient and inpatient DBS procedures performed by a single surgeon between January 2018 and November 2022. The main outcome measures used for comparison between the 2 groups were total complications, length of stay, rate of postoperative infection, postoperative hemorrhage rate, 30-day emergency department (ED) visits and readmissions, and IV antihypertensive requirement. RESULTS: A total of 44 outpatient DBS surgeries were compared with 70 inpatient DBS surgeries. The outpatient DBS cohort had a shorter mean postoperative stay (4.19 vs 39.59 hours, P = .0015), lower total complication rate (2.3% vs 12.8%, P = .1457), and lower wound infection rate (0% vs 2.9%, P = .52) compared with the inpatient cohort, but the difference in complications was not statistically significant. In the 30-day follow-up period, ED visits were similar between the cohorts (6.8% vs 7.1%, P = .735), but no outpatient DBS patient required readmission, whereas all inpatient DBS patients visiting the ED were readmitted ( P = .155). CONCLUSION: Our study demonstrates that DBS can be safely performed on an outpatient basis with same-day hospital discharge and close continuous monitoring.

Single neurons in the human medial temporal lobe flexibly shift representations across spatial and memory tasks.

Investigations into how individual neurons encode behavioral variables of interest have revealed specific representations in single neurons, such as place and object cells, as well as a wide range of cells with conjunctive encodings or mixed selectivity. However, as most experiments examine neural activity within individual tasks, it is currently unclear if and how neural representations change across different task contexts. Within this discussion, the medial temporal lobe is particularly salient, as it is known to be important for multiple behaviors including spatial navigation and memory, however the relationship between these functions is currently unclear. Here, to investigate how representations in single neurons vary across different task contexts in the MTL, we collected and analyzed single-neuron activity from human participants as they completed a paired-task session consisting of a passive-viewing visual working memory and a spatial navigation and memory task. Five patients contributed 22 paired-task sessions, which were spike sorted together to allow for the same putative single neurons to be compared between the different tasks. Within each task, we replicated concept-related activations in the working memory task, as well as target-location and serial-position responsive cells in the navigation task. When comparing neuronal activity between tasks, we first established that a significant number of neurons maintained the same kind of representation, responding to stimuli presentations across tasks. Further, we found cells that changed the nature of their representation across tasks, including a significant number of cells that were stimulus responsive in the working memory task that responded to serial position in the spatial task. Overall, our results support a flexible encoding of multiple, distinct aspects of different tasks by single neurons in the human MTL, whereby some individual neurons change the nature of their feature coding between task contexts.

Magnetic resonance imaging-guided stereotactic laser ablation therapy for the treatment of pediatric epilepsy: a retrospective multiinstitutional study.

OBJECTIVE: The authors of this study evaluated the safety and efficacy of stereotactic laser ablation (SLA) for the treatment of drug-resistant epilepsy (DRE) in children. METHODS: Seventeen North American centers were enrolled in the study. Data for pediatric patients with DRE who had been treated with SLA between 2008 and 2018 were retrospectively reviewed. RESULTS: A total of 225 patients, mean age 12.8 ± 5.8 years, were identified. Target-of-interest (TOI) locations included extratemporal (44.4%), temporal neocortical (8.4%), mesiotemporal (23.1%), hypothalamic (14.2%), and callosal (9.8%). Visualase and NeuroBlate SLA systems were used in 199 and 26 cases, respectively. Procedure goals included ablation (149 cases), disconnection (63), or both (13). The mean follow-up was 27 ± 20.4 months. Improvement in targeted seizure type (TST) was seen in 179 (84.0%) patients. Engel classification was reported for 167 (74.2%) patients; excluding the palliative cases, 74 (49.7%), 35 (23.5%), 10 (6.7%), and 30 (20.1%) patients had Engel class I, II, III, and IV outcomes, respectively. For patients with a follow-up ≥ 12 months, 25 (51.0%), 18 (36.7%), 3 (6.1%), and 3 (6.1%) had Engel class I, II, III, and IV outcomes, respectively. Patients with a history of pre-SLA surgery related to the TOI, a pathology of malformation of cortical development, and 2+ trajectories per TOI were more likely to experience no improvement in seizure frequency and/or to have an unfavorable outcome. A greater number of smaller thermal lesions was associated with greater improvement in TST. Thirty (13.3%) patients experienced 51 short-term complications including malpositioned catheter (3 cases), intracranial hemorrhage (2), transient neurological deficit (19), permanent neurological deficit (3), symptomatic perilesional edema (6), hydrocephalus (1), CSF leakage (1), wound infection (2), unplanned ICU stay (5), and unplanned 30-day readmission (9). The relative incidence of complications was higher in the hypothalamic target location. Target volume, number of laser trajectories, number or size of thermal lesions, or use of perioperative steroids did not have a significant effect on short-term complications. CONCLUSIONS: SLA appears to be an effective and well-tolerated treatment option for children with DRE. Large-volume prospective studies are needed to better understand the indications for treatment and demonstrate the long-term efficacy of SLA in this population.

Task Modulation of Single-Neuron Activity in the Human Amygdala and Hippocampus.

The human amygdala and hippocampus are critically involved in various processes in face perception. However, it remains unclear how task demands or evaluative contexts modulate processes underlying face perception. In this study, we employed two task instructions when participants viewed the same faces and recorded single-neuron activity from the human amygdala and hippocampus. We comprehensively analyzed task modulation for three key aspects of face processing and we found that neurons in the amygdala and hippocampus (1) encoded high-level social traits such as perceived facial trustworthiness and dominance and this response was modulated by task instructions; (2) encoded low-level facial features and demonstrated region-based feature coding, which was not modulated by task instructions; and (3) encoded fixations on salient face parts such as the eyes and mouth, which was not modulated by task instructions. Together, our results provide a comprehensive survey of task modulation of neural processes underlying face perception at the single-neuron level in the human amygdala and hippocampus.